Trial Title:
Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia
NCT ID:
NCT06317662
Condition:
Acute Leukemia of Ambiguous Lineage
B Acute Lymphoblastic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leucovorin
Cytarabine
Dexamethasone
Dexamethasone acetate
Prednisone
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Cortisone
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Methotrexate
Vincristine
Venetoclax
Daunorubicin
Asparaginase
Mercaptopurine
Pegaspargase
Thioguanine
Blinatumomab
Asparaginase erwinia chrysanthemi, recombinant-rywn
Antineoplastic Agents, Immunological
Muromonab-CD3
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Prednisolone hemisuccinate
Prednisolone phosphate
BB 1101
2-Aminopurine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Asparaginase Erwinia chrysanthemi
Description:
Given recombinant crisantaspase IM or crisantaspase IM or IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Safety Phase Cohort
Other name:
Asparaginase Erwinia chrysanthemi (Recombinant)-rywn
Other name:
Asparaginase Erwinia chrysanthemi, Recombinant-rywn
Other name:
Asparaginase Erwinia chrysanthemi-rywn
Other name:
Crisantaspase
Other name:
Crisantaspase Biobetter JZP-458
Other name:
Crisantaspasum
Other name:
Enrylaze
Other name:
Erwinase
Other name:
Erwinaze
Other name:
JZP 458
Other name:
JZP-458
Other name:
JZP458
Other name:
PF743
Other name:
RC-P JZP-458
Other name:
Recombinant Asparaginase erwinia chrysanthemi JZP-458
Other name:
Recombinant Crisantaspase JZP-458
Other name:
Recombinant Erwinia asparaginase JZP-458
Other name:
Rylaze
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Blinatumomab
Description:
Given IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
AMG 103
Other name:
AMG-103
Other name:
AMG103
Other name:
Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
Other name:
Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
Other name:
Blincyto
Other name:
MEDI 538
Other name:
MEDI-538
Other name:
MEDI538
Other name:
MT 103
Other name:
MT-103
Other name:
MT103
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Intervention type:
Drug
Intervention name:
Calaspargase Pegol
Description:
Given IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
Other name:
Asparlas
Other name:
Calaspargase Pegol-mknl
Other name:
EZN-2285
Other name:
SC-PEG E. Coli L-Asparaginase
Other name:
Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Asta B 518
Other name:
B 518
Other name:
B-518
Other name:
B518
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR 138719
Other name:
WR- 138719
Other name:
WR-138719
Other name:
WR138719
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Given IT or IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
.beta.-Cytosine arabinoside
Other name:
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
Other name:
1-.beta.-D-Arabinofuranosylcytosine
Other name:
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Other name:
1-Beta-D-arabinofuranosylcytosine
Other name:
1.beta.-D-Arabinofuranosylcytosine
Other name:
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
Other name:
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Other name:
Alexan
Other name:
Ara-C
Other name:
ARA-cell
Other name:
Arabine
Other name:
Arabinofuranosylcytosine
Other name:
Arabinosylcytosine
Other name:
Aracytidine
Other name:
Aracytin
Other name:
Aracytine
Other name:
Beta-Cytosine Arabinoside
Other name:
CHX-3311
Other name:
Cytarabinum
Other name:
Cytarbel
Other name:
Cytosar
Other name:
Cytosine Arabinoside
Other name:
Cytosine-.beta.-arabinoside
Other name:
Cytosine-beta-arabinoside
Other name:
Erpalfa
Other name:
Starasid
Other name:
Tarabine PFS
Other name:
U 19920
Other name:
U-19920
Other name:
Udicil
Other name:
WR-28453
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
Given IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
Daunomycin
Other name:
Daunorrubicina
Other name:
DNR
Other name:
Leukaemomycin C
Other name:
Rubidomycin
Other name:
Rubomycin C
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given PO or NG or IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
Aacidexam
Other name:
Adexone
Other name:
Aknichthol Dexa
Other name:
Alba-Dex
Other name:
Alin
Other name:
Alin Depot
Other name:
Alin Oftalmico
Other name:
Amplidermis
Other name:
Anemul mono
Other name:
Auricularum
Other name:
Auxiloson
Other name:
Baycadron
Other name:
Baycuten
Other name:
Baycuten N
Other name:
Cortidexason
Other name:
Cortisumman
Other name:
Decacort
Other name:
Decadrol
Other name:
Decadron
Other name:
Decadron DP
Other name:
Decalix
Other name:
Decameth
Other name:
Decasone R.p.
Other name:
Dectancyl
Other name:
Dekacort
Other name:
Deltafluorene
Other name:
Deronil
Other name:
Desamethasone
Other name:
Desameton
Other name:
Dexa-Mamallet
Other name:
Dexa-Rhinosan
Other name:
Dexa-Scheroson
Other name:
Dexa-sine
Other name:
Dexacortal
Other name:
Dexacortin
Other name:
Dexafarma
Other name:
Dexafluorene
Other name:
Dexalocal
Other name:
Dexamecortin
Other name:
Dexameth
Other name:
Dexamethasone Intensol
Other name:
Dexamethasonum
Other name:
Dexamonozon
Other name:
Dexapos
Other name:
Dexinoral
Other name:
Dexone
Other name:
Dinormon
Other name:
Dxevo
Other name:
Fluorodelta
Other name:
Fortecortin
Other name:
Gammacorten
Other name:
Hemady
Other name:
Hexadecadrol
Other name:
Hexadrol
Other name:
LenaDex
Other name:
Lokalison-F
Other name:
Loverine
Other name:
Methylfluorprednisolone
Other name:
Millicorten
Other name:
Mymethasone
Other name:
Orgadrone
Other name:
Spersadex
Other name:
TaperDex
Other name:
Visumetazone
Other name:
ZoDex
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
Given IV
Arm group label:
Arm C
Other name:
Adriablastin
Other name:
Hydroxydaunomycin
Other name:
Hydroxyl Daunorubicin
Other name:
Hydroxyldaunorubicin
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
EC
Intervention type:
Procedure
Intervention name:
FDG-Positron Emission Tomography
Description:
Undergo FDG-PET
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
FDG
Other name:
FDG-PET
Other name:
FDG-PET Imaging
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
Given PO or NG or IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
Folinic acid
Intervention type:
Procedure
Intervention name:
Lumbar Puncture
Description:
Undergo lumbar puncture
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
LP
Other name:
Spinal Tap
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Mercaptopurine
Description:
Given PO or NG
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
3H-Purine-6-thiol
Other name:
6 MP
Other name:
6 Thiohypoxanthine
Other name:
6 Thiopurine
Other name:
6-Mercaptopurine
Other name:
6-Mercaptopurine Monohydrate
Other name:
6-MP
Other name:
6-Purinethiol
Other name:
6-Thiopurine
Other name:
6-Thioxopurine
Other name:
6H-Purine-6-thione, 1,7-dihydro- (9CI)
Other name:
7-Mercapto-1,3,4,6-tetrazaindene
Other name:
Alti-Mercaptopurine
Other name:
Azathiopurine
Other name:
Bw 57-323H
Other name:
Flocofil
Other name:
Ismipur
Other name:
Leukerin
Other name:
Leupurin
Other name:
Mercaleukim
Other name:
Mercaleukin
Other name:
Mercaptina
Other name:
Mercaptopurinum
Other name:
Mercapurin
Other name:
Mern
Other name:
NCI-C04886
Other name:
Puri-Nethol
Other name:
Purimethol
Other name:
Purine, 6-mercapto-
Other name:
Purine-6-thiol (8CI)
Other name:
Purine-6-thiol, monohydrate
Other name:
Purinethiol
Other name:
Purinethol
Other name:
U-4748
Other name:
WR-2785
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
Given IT or IV or PO or NG
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
Abitrexate
Other name:
Alpha-Methopterin
Other name:
Amethopterin
Other name:
Brimexate
Other name:
CL 14377
Other name:
CL-14377
Other name:
Emtexate
Other name:
Emthexat
Other name:
Emthexate
Other name:
Farmitrexat
Other name:
Fauldexato
Other name:
Folex
Other name:
Folex PFS
Other name:
Lantarel
Other name:
Ledertrexate
Other name:
Lumexon
Other name:
Maxtrex
Other name:
Medsatrexate
Other name:
Metex
Other name:
Methoblastin
Other name:
Methotrexate LPF
Other name:
Methotrexate Methylaminopterin
Other name:
Methotrexatum
Other name:
Metotrexato
Other name:
Metrotex
Other name:
Mexate
Other name:
Mexate-AQ
Other name:
MTX
Other name:
Novatrex
Other name:
Rheumatrex
Other name:
Texate
Other name:
Tremetex
Other name:
Trexeron
Other name:
Trixilem
Other name:
WR-19039
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNV Scan
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Drug
Intervention name:
Pegaspargase
Description:
Given IV or IM
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
L-Asparaginase with Polyethylene Glycol
Other name:
Oncaspar
Other name:
Oncaspar-IV
Other name:
PEG-Asparaginase
Other name:
PEG-L-Asparaginase
Other name:
PEG-L-Asparaginase (Enzon - Kyowa Hakko)
Other name:
PEGLA
Other name:
Polyethylene Glycol L-Asparaginase
Other name:
Polyethylene Glycol-L-Asparaginase
Intervention type:
Drug
Intervention name:
Prednisolone
Description:
Given PO or NG
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
(11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione
Other name:
.delta.1-Hydrocortisone
Other name:
Adnisolone
Other name:
Aprednislon
Other name:
Capsoid
Other name:
Cortalone
Other name:
Cortisolone
Other name:
Dacortin H
Other name:
Decaprednil
Other name:
Decortin H
Other name:
Delta(1)Hydrocortisone
Other name:
Delta- Cortef
Other name:
Delta-Cortef
Other name:
Delta-Diona
Other name:
Delta-F
Other name:
Delta-Phoricol
Other name:
Delta1-dehydro-hydrocortisone
Other name:
Deltacortril
Other name:
Deltahydrocortisone
Other name:
Deltasolone
Other name:
Deltidrosol
Other name:
Dhasolone
Other name:
Di-Adreson-F
Other name:
Dontisolon D
Other name:
Estilsona
Other name:
Fisopred
Other name:
Frisolona
Other name:
Gupisone
Other name:
Hostacortin H
Other name:
Hydeltra
Other name:
Hydeltrasol
Other name:
Klismacort
Other name:
Kuhlprednon
Other name:
Lenisolone
Other name:
Lepi-Cortinolo
Other name:
Linola-H N
Other name:
Linola-H-Fett N
Other name:
Longiprednil
Other name:
Metacortandralone
Other name:
Meti Derm
Other name:
Meticortelone
Other name:
Opredsone
Other name:
Panafcortelone
Other name:
Precortisyl
Other name:
Pred-Clysma
Other name:
Predeltilone
Other name:
Predni-Coelin
Other name:
Predni-Helvacort
Other name:
Prednicortelone
Other name:
Prednisolonum
Other name:
Prelone
Other name:
Prenilone
Other name:
Sterane
Intervention type:
Drug
Intervention name:
Prednisone
Description:
Given PO or NG
Arm group label:
Steroid Prephase (prednisone, prednisolone)
Other name:
.delta.1-Cortisone
Other name:
1, 2-Dehydrocortisone
Other name:
Adasone
Other name:
Cortancyl
Other name:
Dacortin
Other name:
DeCortin
Other name:
Decortisyl
Other name:
Decorton
Other name:
Delta 1-Cortisone
Other name:
Delta-Dome
Other name:
Deltacortene
Other name:
Deltacortisone
Other name:
Deltadehydrocortisone
Other name:
Deltasone
Other name:
Deltison
Other name:
Deltra
Other name:
Econosone
Other name:
Lisacort
Other name:
Meprosona-F
Other name:
Metacortandracin
Other name:
Meticorten
Other name:
Ofisolona
Other name:
Orasone
Other name:
Panafcort
Other name:
Panasol-S
Other name:
Paracort
Other name:
Perrigo Prednisone
Other name:
PRED
Other name:
Predicor
Other name:
Predicorten
Other name:
Prednicen-M
Other name:
Prednicort
Other name:
Prednidib
Other name:
Prednilonga
Other name:
Predniment
Other name:
Prednisone Intensol
Other name:
Prednisonum
Other name:
Prednitone
Other name:
Promifen
Other name:
Rayos
Other name:
Servisone
Other name:
SK-Prednisone
Intervention type:
Drug
Intervention name:
Therapeutic Hydrocortisone
Description:
Given IT
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
Aeroseb-HC
Other name:
Barseb HC
Other name:
Barseb-HC
Other name:
Cetacort
Other name:
Cort-Dome
Other name:
Cortef
Other name:
Cortenema
Other name:
Cortifan
Other name:
Cortisol
Other name:
Cortispray
Other name:
Cortril
Other name:
Dermacort
Other name:
Domolene
Other name:
Eldecort
Other name:
Hautosone
Other name:
Heb-Cort
Other name:
Hydrocortisone
Other name:
Hydrocortone
Other name:
Hytone
Other name:
Komed-HC
Other name:
Nutracort
Other name:
Proctocort
Other name:
Rectoid
Intervention type:
Drug
Intervention name:
Thioguanine
Description:
Given PO or NG
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
2-Amino 6MP
Other name:
2-Amino-1,7-dihydro-6H-purine-6-thione
Other name:
2-Amino-6-mercaptopurine
Other name:
2-Amino-6-purinethiol
Other name:
2-Aminopurin-6-thiol
Other name:
2-Aminopurine-6(1H)-thione
Other name:
2-Aminopurine-6-thiol
Other name:
2-Aminopurine-6-thiol Hemihydrate
Other name:
2-Mercapto-6-aminopurine
Other name:
6-Amino-2-mercaptopurine
Other name:
6-Mercapto-2-aminopurine
Other name:
6-Mercaptoguanine
Other name:
6-TG
Other name:
6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
Other name:
BW 5071
Other name:
Lanvis
Other name:
Tabloid
Other name:
Thioguanine Hemihydrate
Other name:
Thioguanine Hydrate
Other name:
Tioguanin
Other name:
Tioguanine
Other name:
Wellcome U3B
Other name:
WR-1141
Other name:
X 27
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO or NG
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Safety Phase Cohort
Other name:
ABT 199
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC 0199
Other name:
GDC-0199
Other name:
GDC0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Given IV
Arm group label:
Arm A
Arm group label:
Arm B, Cohort 1
Arm group label:
Arm B, Cohort 2
Arm group label:
Arm B, Cohort 3
Arm group label:
Arm B, Cohort 4
Arm group label:
Arm C
Arm group label:
Safety Phase Cohort
Other name:
LCR
Other name:
Leurocristine
Other name:
VCR
Other name:
Vincrystine
Summary:
This phase II trial tests the addition of venetoclax and/or blinatumomab to usual
chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL)
with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene
rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell
lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2,
a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may
interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in
different ways to stop the growth of cancer cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or
blinatumomab to standard chemotherapy may be more effective at treating patients with ALL
than standard chemotherapy alone, but it may also cause more side effects. This clinical
trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to
chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of venetoclax in addition to a standard
chemotherapy backbone and two cycles of blinatumomab in infants (aged 365 days or less at
diagnosis) with newly diagnosed KMT2A-R ALL.
II. To determine in a randomized manner if the addition of venetoclax to induction
chemotherapy improves end of induction minimal residual disease (MRD)-negative remission
rates in infants with KMT2A-R ALL.
SECONDARY OBJECTIVES:
I. To compare event free survival (EFS) rates of infants with KMT2A-R ALL treated on arm
B to those treated on arm A.
II. To compare 3-year EFS of infants with KMT2A-R ALL treated on arm A to historical
controls.
III. To determine the feasibility of treating infants with KMT2A-G ALL with a Children's
Oncology Group (COG) high-risk ALL chemotherapy backbone and two cycles of blinatumomab
and describe their outcomes.
IV. To characterize the pharmacokinetics (PK) of venetoclax in infants.
EXPLORATORY OBJECTIVES:
I. To describe 3-year EFS of infants with KMT2A-R ALL treated on arm B. II. To describe
3-year EFS of infants with KMT2A-G ALL treated on arm C. III. To evaluate the use of
high-throughput sequencing (HTS) for MRD detection in infant ALL compared to centralized
flow cytometry.
IV. To characterize the PK of calaspargase pegol-mknl in infants with ALL. V. To report
the incidence of CD19 negative relapse and myeloid switch relapse with protocol therapy.
VI. To evaluate the impact of venetoclax in combination with chemotherapy on T-cell
subsets and function.
VII. To describe the feasibility of T-cell collection and success of T-cell manufacturing
for infants with KMT2A-R ALL who receive chimeric antigen receptor (CAR) T- cell therapy
after coming off protocol therapy.
VIII. To determine predictors of response and resistance to venetoclax and overall
protocol therapy.
IX. To evaluate the impact of subsequent anti-cancer therapy on overall survival after
coming off protocol therapy.
OUTLINE:
STEROID PREPHASE: All patients receive prednisone or prednisolone orally (PO) or
nasogastrically (NG) three times daily (TID) for 7 days prior to the start of induction
therapy (on days 1-7).
Patients who are KMT2A gene rearrangement positive are assigned to the safety phase
cohort. Patients who are KMT2A gene rearrangement negative are assigned to Arm C.
SAFETY PHASE COHORT:
INDUCTION: Patients receive venetoclax PO or NG once daily (QD) on days 1-7, 1-10, or
1-14, daunorubicin intravenously (IV) over 1-15 minutes on days 1 and 2, vincristine IV
on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, pegaspargase
intramuscularly (IM) or IV over 2 hours or calaspargase pegol IV over 1-2 hours on day 4,
and intrathecal therapy (methotrexate, hydrocortisone, cytarabine) intrathecally (IT) on
days 1, 15, and 29 or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology
in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab
block 1 on the next day or when absolute neutrophil counts (ANC) >= 500/uL and platelets
>= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of
induction proceed to blinatumomab block 1 as soon as marrow results are known,
irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and
29. Patients who are MRD > 1% or who have residual non-central nervous system (CNS)
extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol
therapy. All other patients proceed directly to consolidation on the next day or when
peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
cytarabine subcutaneously (SC) QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and
36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on
day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56)
discontinue protocol therapy. All other patients proceed directly to MARMA the next day
or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate
IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV on days 3-4 and 10-11,
intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days
22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2
hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to
blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and
platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal
therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients
proceed directly to delayed intensification the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days
1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and
22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over
15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, and intrathecal therapy
IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed
directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL
and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle,
methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of
each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12
weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease
progression or unacceptable toxicity.
EXPANSION PHASE: After completion of Safety phase, patients who are KMT2A gene
rearrangement positive are randomized to Arm A or Arm B.
ARM A:
INDUCTION: Patients receive daunorubicin IV over 1-15 minutes on days 1 and 2, cytarabine
SC or IV over 15-30 minutes on days 1-14, vincristine IV on days 1, 8, 15, and 22,
dexamethasone PO, NG, or IV TID on days 1-28, pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15,
and 29, or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone
marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the
next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by
morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as
soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and
29. Patients who are MRD > 1% or who have residual non-CNS extramedullary disease at the
end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients
proceed directly to consolidation on the next day or when peripheral counts recover to
ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39,
mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29.
Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue
protocol therapy. All other patients proceed directly to MARMA the next day or when
peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate
IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV on days 3-4 and 10-11,
intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days
22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2
hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to
blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and
platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal
therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients
proceed directly to delayed intensification the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days
1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and
22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over
15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, and intrathecal therapy
IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed
directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL
and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle,
methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of
each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12
weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease
progression or unacceptable toxicity.
ARM B: Patients are assigned to 1 of 4 cohorts.
COHORT 1:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over
1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO,
NG, or IV TID on days 1-28, pegaspargase IM or IV over 2 hours or calaspargase pegol IV
over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8,
15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of
induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC
>= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the
bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow
results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and
29. Patients who are MRD > 1% or who have residual non-CNS extramedullary disease at the
end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients
proceed directly to consolidation on the next day or when peripheral counts recover to
ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39,
mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29.
Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue
protocol therapy. All other patients proceed directly to MARMA the next day or when
peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA + VENETOCLAX: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose
methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV on days 3-4 and
10-11, intrathecal therapy IT on days 1 and 8, venetoclax PO or NG QD, high dose
cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or
crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49),
all patients proceed directly to blinatumomab block 2 the next day or when peripheral
counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal
therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients
proceed directly to delayed intensification the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days
1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and
22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over
15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over
15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end
of delayed intensification (day 63), all patients proceed directly to maintenance the
next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle,
methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of
each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12
weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease
progression or unacceptable toxicity.
COHORT 2:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over
1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO,
NG, or IV TID on days 1-28, pegaspargase IM or IV over 2 hours or calaspargase pegol IV
over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8,
15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of
induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC
>= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the
bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow
results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and
29. Patients who are MRD > 1% or who have residual non-CNS extramedullary disease at the
end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients
proceed directly to consolidation on the next day or when peripheral counts recover to
ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION + VENETOCLAX: Patients receive venetoclax PO or NG QD, cyclophosphamide IV
over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days
1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and
intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of
consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed
directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and
platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate
IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV on days 3-4 and 10-11,
intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days
22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2
hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to
blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and
platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal
therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients
proceed directly to delayed intensification the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days
1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and
22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over
15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over
15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end
of delayed intensification (day 63), all patients proceed directly to maintenance the
next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle,
methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of
each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12
weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease
progression or unacceptable toxicity.
COHORT 3:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over
1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO,
NG, or IV TID on days 1-28, pegaspargase IM or IV over 2 hours or calaspargase pegol IV
over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8,
15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of
induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC
>= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the
bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow
results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and
29. Patients who are MRD > 1% or who have residual non-CNS extramedullary disease at the
end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients
proceed directly to consolidation on the next day or when peripheral counts recover to
ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION + VENETOCLAX: Patients receive venetoclax PO or NG QD, cyclophosphamide IV
over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days
1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and
intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of
consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed
directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and
platelets >= 75,000/uL.
MARMA + VENETOCLAX: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose
methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV on days 3-4 and
10-11, intrathecal therapy IT on days 1 and 8, venetoclax PO or NG QD, high dose
cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or
crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49),
all patients proceed directly to blinatumomab block 2 the next day or when peripheral
counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal
therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients
proceed directly to delayed intensification the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days
1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and
22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over
15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over
15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end
of delayed intensification (day 63), all patients proceed directly to maintenance the
next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle,
methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of
each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12
weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease
progression or unacceptable toxicity.
COHORT 4:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over
1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO,
NG, or IV TID on days 1-28, pegaspargase IM or IV over 2 hours or calaspargase pegol IV
over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8,
15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of
induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC
>= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the
bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow
results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and
29. Patients who are MRD > 1% or who have residual non-CNS extramedullary disease at the
end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients
proceed directly to consolidation on the next day or when peripheral counts recover to
ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39,
mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29.
Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue
protocol therapy. All other patients proceed directly to MARMA the next day or when
peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate
IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV on days 3-4 and 10-11,
intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days
22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2
hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to
blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and
platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal
therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients
proceed directly to delayed intensification the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days
1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and
22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over
15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over
15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end
of delayed intensification (day 63), all patients proceed directly to maintenance the
next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle,
methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of
each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12
weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease
progression or unacceptable toxicity.
ARM C:
INDUCTION: Patients receive daunorubicin IV over 1-15 minutes on days 1 and 2, cytarabine
SC or IV over 15-30 minutes on days 1-14, vincristine IV on days 1, 8, 15, and 22,
dexamethasone PO, NG, or IV TID on days 1-28, pegaspargase IM or IV over 2 hours or
calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15,
and 29, or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone
marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the
next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by
morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as
soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and
8, blinatumomab IV on days 1-28, 1-7, or 8-28, and methotrexate IT on days 15 and 29.
Patients who are MRD > 1% or who have residual non-CNS extramedullary disease at the end
of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed
directly to consolidation on the next day or when peripheral counts recover to ANC >=
750/uL and platelets >= 75,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39,
mercaptopurine PO or NG QD on days 1-14 and 29-42, methotrexate IT on days 8, 15, and 22,
vincristine IV on days 15, 22, 43, and 50, and pegaspargase IM or IV over 2 hours of
calaspargase pegol IV over 1-2 hours on days 15 and 43. Patients who are MRD >= 0.01% at
the end of consolidation therapy (day 56) discontinue protocol therapy. All other
patients proceed directly to interim maintenance 1 the next day or when peripheral counts
recover to ANC >= 750/uL and platelets >= 75,000/uL.
INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high
dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, mercaptopurine PO or NG on
days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on days 1 and 29, and leucovorin PO
or NG or IV on days 3-4, 17-18, 31-32, and 45-46. At the end of interim maintenance 1
(day 63), all patients proceed directly to blinatumomab block 2 the next day or when
peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28, and methotrexate IT
on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed
directly to delayed intensification the next day or when peripheral counts recover to ANC
>= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive methotrexate IT on days 1, 29, and 36,
dexamethasone PO, NG, or IV TID on days 1-7 and 15-21, vincristine IV on days 1, 8, 15,
43, and 50, doxorubicin IV over 3-15 minutes on days 1, 8, and 15, pegaspargase IM or IV
over 2 hours or calaspargase pegol IV over 1-2 hours on days 4 and 43, cyclophosphamide
IV over 30-60 minutes on day 29, thioguanine PO or NG on days 29-42, and cytarabine SC or
IV over 15-30 minutes on days 29-32 and 36-39. At the end of delayed intensification (day
63), all patients proceed directly to interim maintenance 2 the next day or when
peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31, and 41,
methotrexate IV push over 2-5 minutes of IV over 10-15 minutes on days 1, 11, 21, 31, and
41, methotrexate IT on days 1 and 31, and pegaspargase IM or IV over 2 hours on days 2
and 22 or calaspargase pegol IV over 1-2 hours on days 2 and 23. At the end of interim
maintenance 2 (day 56), all patients proceed directly to maintenance the next day or when
peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MAINTENANCE: Patients receive methotrexate IT on day 1 of each cycle, vincristine IV on
day 1 of each cycle, prednisone or prednisolone PO, NG, or IV BID on days 1-5 of each
cycle, mercaptopurine PO or NG on days 1-84 of each cycle, and methotrexate PO, NG, or IV
on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle. Cycles repeat
every 12 weeks (84 days) for up to 2 years from the start of interim maintenance 1 in the
absence of disease progression or unacceptable toxicity.
All patients undergo bone marrow aspiration and collection of blood samples throughout
the trial and undergo ECHO or MUGA at screening and end of therapy. Patients may undergo
CT, MRI, FDG-PET, and/or lumbar puncture if clinically indicated.
After completion of study treatment, patients are followed up for up to 3 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- All patients must be enrolled on APEC14B1 and consented to eligibility screening
(part A) prior to treatment and enrollment on AALL2321
- Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must
be > 36 weeks gestational age at the time of enrollment
- Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World
Health Organization [WHO] classification), also termed B-precursor ALL, or acute
leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia.
For patients with ALAL, the immunophenotype of the leukemia must comprise at least
50% B lineage
- Diagnostic immunophenotype: Leukemia cells must express CD19
Exclusion Criteria:
- Patients with Down Syndrome
- Patients with secondary B-ALL that developed after treatment of a prior malignancy
with cytotoxic chemotherapy
- Patients must not have received any cytotoxic chemotherapy for either the current
diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of
protocol therapy, with the exception of:
- Steroid pretreatment:
- PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in
the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or
methylPREDNISolone does not affect eligibility
- Inhaled and topical steroids are not considered pretreatment
- Note: Pretreatment with dexamethasone in the 28 days prior to initiation
of protocol therapy is not allowed with the exception of a single dose of
dexamethasone used during or within 6 hours prior to or after sedation to
prevent or treat airway edema. However, prior exposure to ANY steroids
that occurred > 28 days before enrollment does not affect eligibility
- Intrathecal cytarabine or methotrexate:
- An intrathecal dose of cytarabine or methotrexate in the 7 days prior to
enrollment does not affect eligibility
- Note: The preference is to defer the diagnostic lumbar puncture with
intrathecal chemotherapy to day 1 of induction to allow for cytoreduction
of circulating blasts and decrease the potential for central nervous
system (CNS) contamination due to a traumatic tap. If done prior to day 1
of induction, these results will be used to determine CNS status
- Hydroxyurea:
- Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior
to enrollment does not affect eligibility
- All patients and/or their parents or legal guardians must sign a written informed
consent
- All institutional, Food and Drug Administration (FDA) and National Cancer Institute
(NCI) requirements for human studies must be met
Gender:
All
Minimum age:
N/A
Maximum age:
365 Days
Healthy volunteers:
No
Start date:
January 26, 2025
Completion date:
December 31, 2028
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06317662
