Trial Title:
A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL)
NCT ID:
NCT06124157
Condition:
B Acute Lymphoblastic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Philadelphia Chromosome
Leucovorin
Cytarabine
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
Daunorubicin
Asparaginase
Dasatinib
Mercaptopurine
Pegaspargase
Thioguanine
Blinatumomab
Antineoplastic Agents, Immunological
Muromonab-CD3
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Prednisolone hemisuccinate
Prednisolone phosphate
2-Aminopurine
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and CSF sample collection
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Blinatumomab
Description:
Receive IV
Arm group label:
Arm II (blinatumomab)
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 Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Drug
Intervention name:
Calaspargase Pegol
Description:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Drug
Intervention name:
Cyclophosphamide
Description:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Dasatinib
Description:
Receive PO or NG
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
Other name:
BMS 354825
Other name:
BMS-354825
Other name:
BMS354825
Other name:
Dasatinib Hydrate
Other name:
Dasatinib Monohydrate
Other name:
Sprycel
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Doxorubicin
Description:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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 I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
Other name:
EC
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
Receive PO or IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
Other name:
Folinic acid
Intervention type:
Drug
Intervention name:
Mercaptopurine
Description:
Receive PO
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Receive IT or IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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 I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Receive PO
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Receive PO
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
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:
Radiation
Intervention name:
Radiation Therapy
Description:
Undergo radiation therapy
Arm group label:
Arm II (blinatumomab)
Other name:
Cancer Radiotherapy
Other name:
Energy Type
Other name:
ENERGY_TYPE
Other name:
Irradiate
Other name:
Irradiated
Other name:
Irradiation
Other name:
Radiation
Other name:
Radiation Therapy, NOS
Other name:
Radiotherapeutics
Other name:
Radiotherapy
Other name:
RT
Other name:
Therapy, Radiation
Intervention type:
Drug
Intervention name:
Thioguanine
Description:
Receive PO
Arm group label:
Arm II (blinatumomab)
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:
Vincristine
Description:
Receive IV
Arm group label:
Arm I (dasatinib, standard chemo)
Arm group label:
Arm II (blinatumomab)
Other name:
LCR
Other name:
Leurocristine
Other name:
VCR
Other name:
Vincrystine
Summary:
This phase III trial compares the effect of the combination of blinatumomab with
dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for
treating patients with Philadelphia chromosome positive (PH+) or Philadelphia
chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL).
Blinatumomab is a bispecific antibody that binds to two different proteins-one on the
surface of cancer cells and one on the surface of cells in the immune system. An antibody
is a protein made by the immune system to help fight infections and other harmful
processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which
plays a key role in the immune system's fighting response) at the same time. Blinatumomab
may strengthen the immune system's ability to fight cancer cells by activating the body's
own immune cells to destroy the tumor. Dasatinib is in a class of medications called
tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that
signals cancer cells to multiply, which may help keep cancer cells from growing. Giving
blinatumomab and dasatinib in combination with standard chemotherapy may work better in
treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and
chemotherapy alone.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare the 4-year event free survival (EFS) of children, adolescents, and young
adults with Ph+ (BCR:ABL1-rearranged) and Ph-like ABL-class B- ALL who are randomized
post-Induction to receive continuous dasatinib and the modified augmented
Berlin-Frankfurt-Munster (mBFM) chemotherapy backbone (Arm A) versus continuous dasatinib
and a chemotherapy backbone that incorporates three cycles of blinatumomab (Arm B)
without traditional consolidation chemotherapy.
SECONDARY OBJECTIVES:
I. To compare the 4-year and long-term overall survival (OS) of all patients with Ph+ and
Ph-like ABL-class B-ALL between randomized arms.
I. To compare post-induction/pre-maintenance toxicities (infections, mucositis,
neurotoxicity, cytokine release syndrome, therapy delays > 14 days, and treatment-related
mortality) between patients on the randomized study arms.
I. To compare end of consolidation (EOC)/timepoint 2 (TP2) minimal residual disease (MRD)
negativity at the 1x10^-4 or 0.01% threshold between patients on the randomized study
arms.
EXPLORATORY OBJECTIVES:
I. To describe rates of end of induction (EOI)/timepoint 1 (TP1) bone marrow MRD
negativity with the introduction of dasatinib by induction day 15 for Ph+ and Ph-like
ABL-class B-ALL patients as a whole cohort and as separate groups.
II. To describe EFS, disease-free survival (DFS), and overall survival (OS) of Ph+ and
Ph-like ABL-class B-ALL patients separately and compared to historical controls.
III. To describe the outcomes of patients with Ph+ and Ph-like ABL-class B-ALL who are
removed from protocol therapy due to consolidation failure.
IV. To describe the percentage of patients with Ph+ and Ph-like ABL-class B-ALL who
continue tyrosine kinase inhibitors (TKI) beyond protocol-prescribed therapy and their
outcomes.
V. To describe the prognostic significance of MRD by next-generation sequencing (NGS) at
end of induction and end of consolidation.
VI. To describe the clinical characteristics and outcomes of patients with chronic
myeloid leukemia (CML)-like biology.
VII. To describe the immune function of Ph+ and Ph-like ABL-class B-ALL patients between
the two randomized arms and correlate with treatment response.
VIII. To describe the dasatinib levels in the plasma and cerebrospinal fluid of children
with Ph+ and Ph-like ABL-class B-ALL and correlate with outcome.
IX. To describe the impact of dasatinib and high-dose methotrexate interaction and
identify clinical and biologic factors influencing methotrexate clearance.
OUTLINE:
INDUCTION PART I: All patients receive dasatinib orally (PO) or nasogastrically (NG) once
daily (QD) days 1-14 per standard of care (SOC).
Patients are randomized to 1 of 2 arms.
ARM I: INDUCTION PART II: Patients receive dasatinib PO or NG QD on days 15-29,
daunorubicin intravenously (IV) over 15 minutes on days 15 and 22, prednisolone or
prednisone PO twice daily (BID) on days 1-28, vincristine IV on days 15 and 22,
methotrexate intrathecally (IT) on days 15, 22, and 29, and cytarabine IT on days 18 and
25 for 2 weeks on study.
CONSOLIDATION PART I: Patients receive dasatinib PO or NG QD on days 1-28,
cyclophosphamide IV over 30-60 minutes on day 1, cytarabine IV over 30 minutes on says
1-4 and 8-11, mercaptopurine PO QD on days 1-14, methotrexate IT on days 1, 8, 15 and 22,
pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 15, and vincristine IV on
days 1 and 22 over 4 weeks on study.
CONSOLIDATION PART II: Patients receive dasatinib PO or NG QD on day 29 until the end of
consolidation, cyclophosphamide IV over 30-60 minutes on day 29, cytarabine IV over 30
minutes on days 29-32 and 36-39, mercaptopurine PO QD on days 29-42, methotrexate IT on
days 1, 8, 15 and 22, pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 43,
and vincristine IV on days 43 and 50 over 4 weeks on study.
INTERIM MAINTENANCE I: Patients receive dasatinib PO or NG QD until the end of interim
maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and
50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8,
22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9
weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive dasatinib PO or NG QD on days 1-28,
methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV
over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and
pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 9 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive dasatinib PO or NG QD on day 29 until
the end of delayed intensification part II, cyclophosphamide IV over 60 minutes on day
29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and
36, thioguanine PO on days 29-42, pegaspargase IV or calaspargase pegol on day 43 and
vincristine IV on days 43 and 50 over 9 weeks on study.
INTERIM MAINTENANCE PART II: Patients receive dasatinib PO or NG QD on day 1 until the
end of interim maintenance part II, methotrexate IV on days 1, 11, 21, 31, and 41,
vincristine IV on 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and
pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 and 23 over 9 weeks
on study.
MAINTENANCE: Patients receive dasatinib PO or NG QD on days 1-84, methotrexate IT on days
1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on
days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22,
29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years in
the absence of disease progression or unacceptable toxicity.
ARM II: INDUCTION PART II: Patients receive dasatinib PO or NG QD on days 15-29,
daunorubicin intravenously (IV) over 15 minutes on days 15 and 22, prednisolone or
prednisone PO BID on days 1-28, vincristine IV on days 15 and 22 methotrexate IT on days
15, 22, and 29 and cytarabine IT on days 18 and 25 over 2 weeks on study.
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on days 1 and 8,
blinatumomab IV on days 1-28, dasatinib PO or NG on days 1-35, and methotrexate IT on
days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD
fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV
on days 1-28, dasatinib PO or NG on days 1-35, and methotrexate IT on days 1 and 15 over
5 weeks on study.
INTERIM MAINTENANCE I: Patients receive dasatinib PO or NG QD until the end of interim
maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and
50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8,
22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9
weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, dasatinib PO or NG
on days 1-35, and methotrexate IT on day 1 over 9 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive dasatinib PO or NG QD on days 1-28,
methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV
over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and
pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 9 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive dasatinib PO or NG QD on day 29 until
the end of delayed intensification part II, cyclophosphamide IV over 60 minutes on day
29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and
36, thioguanine PO on days 29-42, pegaspargase IV or calaspargase pegol over 1-2 hours on
day 43 and vincristine IV on days 43 and 50 over 9 weeks on study.
INTERIM MAINTENANCE II: Patients receive dasatinib PO or NG QD until the end of interim
maintenance II, methotrexate IV over 15 minutes on days 1, 11, 21, 31, and 41,
vincristine IV on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and
pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2 and 23 over 9 weeks on
study.
All patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during
screening. Patients also undergo blood and cerebrospinal fluid (CSF) sample collection
and bone marrow biopsy throughout the study and as clinically indicated on study.
MAINTENANCE: Patients receive dasatinib PO or NG QD on days 1-84, methotrexate IT on days
1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on
days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22,
29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years in
the absence of disease progression or unacceptable toxicity.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must be > 365 days and < 18 years (for AIEOP-BFM), > 365 days and < 22
years (for COG) and > 365 days and < 46 years (for ALLTogether sites) at the time of
enrollment
- Newly-diagnosed Ph+ or Ph-like ABL-class B-ALL. Leukemic blasts must express CD19.
ABL-class fusions are defined as those involving the following genes predicted to be
sensitive to dasatinib: ABL1, ABL2, CSF1R, KIT, PDGFRA, and PDGFRB
- Evidence of ABL-class fusions including BCR::ABL1 should be documented by a
clinically-validated assay prior to study entry on Day 15 from the first dose of
vinCRIStine during Induction therapy. Accepted methods of detection include
fluorescence in situ hybridization (FISH) using break-apart of colocalization signal
probes, singleplex or multiplex reverse-transcription polymerase chain reaction
(RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing
(e.g., TruSight RNA Pan-Cancer Panel, Illumina, San Diego, CA, USA or equivalent).
Confirmation of 5' fusion partner genes is not required for study enrollment
- Patients must have previously started Induction therapy, which includes vincristine,
a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline,
and/or other standard cytotoxic chemotherapy
- Patients have not received more than 14 days of systemic Induction therapy beginning
with the first Induction dose of vincristine
- Patients may have started dasatinib prior to study entry but cannot have received
more than 14 days of dasatinib
- Patients must have a performance status corresponding to Eastern Cooperative
Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥
50%. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years
of age
- For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50
mL/min/1.73 m^2, as determined by one of the following methods (performed within 7
days prior to enrollment unless otherwise indicated):
- Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m^2
- Measured GFR ≥ 50 mL/min/1.73 m^2 (any age). If measured GFR is used, it must
be performed using direct measurement with a nuclear blood sampling method or
small molecule clearance method (iothalamate or other molecule per
institutional standard)
- For adult patients (age 18 years or older):
- Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault
formula. The creatinine value used in the calculation must have been obtained
within 28 days prior to registration. Estimated creatinine clearance is based
on body weight
- Direct bilirubin < 2.0 mg/dL (34.2 micromoles/L) (within 7 days prior to enrollment
unless otherwise indicated)
- Shortening fraction of ≥ 27% by echocardiogram or
- Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or
echocardiogram AND
- Corrected QT Interval, QTc < 480mSec (within 7 days prior to enrollment unless
otherwise indicated)
- Note: Repeat echocardiogram and electrocardiogram are not required if they were
performed at or after initial ALL diagnosis before study enrollment. (within 7
days prior to enrollment unless otherwise indicated)
Exclusion Criteria:
- Known history of chronic myeloid leukemia (CML)
- ALL developing after a previous cancer treated with cytotoxic chemotherapy
- Active, uncontrolled infection or active systemic illness that requires ongoing
vasopressor support or mechanical ventilation
- Down syndrome (trisomy 21)
- Pregnancy and breast feeding.
- Female patients who are pregnant since fetal toxicities and teratogenic effects
have been noted for several of the study drugs. A negative pregnancy test is
required for female patients of childbearing potential within 7 days prior to
enrollment.
- Lactating females who plan to breastfeed their infants.
- Sexually active male and female patients of reproductive potential who have not
agreed to use an effective contraception method for the duration of treatment
according to protocol
- NOTE: Females of reproductive potential must use effective contraception
during protocol treatment and for 30 days after the last dasatinib dose or
per institutional standard of care for multiagent chemotherapy, whichever
is longer
- Patients with congenital long QT syndrome, history of ventricular arrhythmias, or
heart block
- Prior treatment with any TKI other than dasatinib
- Patients with known Charcot-Marie-Tooth disease
- Patients with significant central nervous system pathology that would preclude
treatment with blinatumomab, including history of severe neurologic disorder or
autoimmune disease with CNS involvement.
- Note: Patients with a history of seizures that are well controlled on stable
doses of anti-epileptic drugs are eligible. Patients with a history of
cerebrovascular ischemia/hemorrhage with residual deficits are not eligible.
Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible
provided all neurologic deficits have resolved
- Human immunodeficiency virus (HIV)-infected patients are eligible if on effective
anti-retroviral therapy that does not interact with planned study agents and with
undetectable viral load within 6 months of treatment
- 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:
366 Days
Maximum age:
46 Years
Healthy volunteers:
No
Start date:
February 28, 2025
Completion date:
December 1, 2030
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/NCT06124157
