Trial Title:
Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases
NCT ID:
NCT06013423
Condition:
Acute Leukemia of Ambiguous Lineage
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Blastic Plasmacytoid Dendritic Cell Neoplasm
Hematopoietic and Lymphoid System Neoplasm
Mixed Phenotype Acute Leukemia
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Non-Hodgkin Lymphoma
Chronic Myeloid Leukemia, BCR-ABL1 Positive
Conditions: Official terms:
Leukemia
Neoplasms
Leukemia, Myeloid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Myeloproliferative Disorders
Acute Disease
Cyclosporine
Mycophenolic Acid
Cyclophosphamide
Thiotepa
Fludarabine
Fludarabine phosphate
Cyclosporins
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspirate
Description:
Undergo bone marrow aspirate
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
BONE MARROW, LIQUID
Other name:
Human Bone Marrow Aspirate
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Receive IV
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
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:
Asta B 518
Other name:
B-518
Other name:
WR-138719
Intervention type:
Drug
Intervention name:
Cyclosporine
Description:
Receive IV or PO
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
27-400
Other name:
Ciclosporin
Other name:
CsA
Other name:
Cyclosporin
Other name:
Cyclosporin A
Other name:
Cyclosporine Modified
Other name:
Gengraf
Other name:
Neoral
Other name:
OL 27-400
Other name:
Sandimmune
Other name:
SangCya
Intervention type:
Procedure
Intervention name:
Diagnostic Imaging
Description:
Undergo diagnostic imaging
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
Medical Imaging
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
EC
Intervention type:
Drug
Intervention name:
Fludarabine Phosphate
Description:
Receive IV
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
2-F-ara-AMP
Other name:
9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
Other name:
Beneflur
Other name:
Fludara
Other name:
SH T 586
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
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:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Drug
Intervention name:
Mycophenolate Mofetil
Description:
Receive IV
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
CellCept
Other name:
MMF
Intervention type:
Other
Intervention name:
Survey Administration
Description:
Ancillary studies
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Intervention type:
Drug
Intervention name:
Thiotepa
Description:
Receive IV
Arm group label:
Arm II (myeloablative UCBT)
Other name:
1,1',1''-Phosphinothioylidynetrisaziridine
Other name:
Girostan
Other name:
N,N', N''-Triethylenethiophosphoramide
Other name:
Oncotiotepa
Other name:
STEPA
Other name:
Tepadina
Other name:
TESPA
Other name:
Tespamin
Other name:
Tespamine
Other name:
Thio-Tepa
Other name:
Thiofosfamide
Other name:
Thiofozil
Other name:
Thiophosphamide
Other name:
Thiophosphoramide
Other name:
Thiotef
Other name:
Tifosyl
Other name:
TIO TEF
Other name:
Tio-tef
Other name:
Triethylene Thiophosphoramide
Other name:
Triethylenethiophosphoramide
Other name:
Tris(1-aziridinyl)phosphine sulfide
Other name:
TSPA
Other name:
WR 45312
Intervention type:
Radiation
Intervention name:
Total-Body Irradiation
Description:
Undergo high-dose or middle-intensity TBI
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
SCT_TBI
Other name:
TBI
Other name:
Total Body Irradiation
Other name:
Whole Body
Other name:
Whole Body Irradiation
Other name:
Whole-Body Irradiation
Intervention type:
Procedure
Intervention name:
Umbilical Cord Blood Transplantation
Description:
Undergo UCBT
Arm group label:
Arm I (myeloablative UCBT)
Arm group label:
Arm II (myeloablative UCBT)
Other name:
Cord Blood
Other name:
Cord Blood Transplantation
Other name:
UCB transplantation
Other name:
UMBILICAL CORD BLOOD TRANSPLANT
Summary:
This phase II trial studies how well giving an umbilical cord blood transplant together
with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating
patients with hematologic diseases. Giving chemotherapy, such as cyclophosphamide,
fludarabine and thiotepa, and TBI before a donor cord blood transplant (CBT) helps stop
the growth of cancer and abnormal cells and helps stop the patient's immune system from
rejecting the donor's stem cells. When the healthy stem cells from a donor are infused
into the patient they may help the patient's bone marrow make stem cells, red blood
cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor
can make an immune response against the body's normal cells. Giving cyclosporine and
mycophenolate mofetil after transplant may stop this from happening in patients with
high-risk hematologic diseases.
Detailed description:
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients aged 6 months through 30 years old receive myeloablative conditioning
comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6,
cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on
days -4 to -1. Patients then undergo UCBT on day 0. Patients undergo blood sample
collection throughout the study. Patients undergo echocardiography (ECHO) or multigated
acquisition scan (MUGA) and diagnostic imaging during screening and as clinically
indicated on study. Patients also undergo blood sample collection and bone marrow
aspirate during screening and on study.
ARM II: Patients aged 6 months through 65 years old receive myeloablative conditioning
comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day
-6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily
(QD) on days -2 and -1. Patients undergo ECHO or MUGA and diagnostic imaging during
screening and as clinically indicated on study. Patients also undergo blood sample
collection and bone marrow aspirate during screening and on study.
Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12
hours, then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day
101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then
PO (if tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered
to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered
over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred
> day 30) after engraftment if there continues to be no evidence of acute GVHD.
After completion of study treatment, patients are followed up at day 180, 1 year, and 2
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients aged 6 months to =< 65 years at time of consent.
- Acute myelogenous leukemia (AML):
- Complete first remission (CR1), complete second remission (CR2) or greater
(CR2+), must have < 5% marrow blasts at the time of transplant.
- Patients in morphologic remission with persistent cytogenetic, flow cytometric,
or molecular aberrations are eligible.
- Acute lymphoblastic leukemia (ALL):
- Complete first remission (CR1) at high risk for relapse such as any of the
following:
- Presence of any high-risk cytogenetic abnormalities such as t(9;22),
t(1;19), t(4;11) or other MLL rearrangements (11q23) or other high-risk
molecular abnormality.
- Failure to achieve MRD- complete remission after induction therapy.
- Persistence or recurrence of minimal residual disease on therapy.
- Any patient unable to tolerate consolidation and/or maintenance
chemotherapy as would have been deemed appropriate by the treating
physician.
- Other high-risk features not defined above.
- Complete second remission (CR2) or greater (CR2+).
- Note: ALL with less than 5% blasts at time of transplant but persistent
cytogenetic, flow cytometric or molecular aberrations are eligible.
- Other acute leukemias: Acute leukemias of ambiguous lineage or mixed phenotype with
less than 5% blasts. Leukemias in morphologic remission with persistent cytogenetic,
flow cytometric or molecular aberrations are eligible.
- Chronic Myeloid Leukemia (CML): Excluding refractory blast crisis. To be eligible in
first chronic phase (CP1) patient must have failed or be intolerant to tyrosine
kinase inhibitor therapy.
- Myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) other than
myelofibrosis:
- MDS/MPD overlap syndromes without myelofibrosis.
- MDS/ MPD patients must have less than 10% bone marrow myeloblasts and absolute
neutrophil count (ANC) > 0.2 (growth factor supported if necessary) at
transplant work-up.
- Non-Hodgkin lymphoma (NHL) at high-risk of relapse or progression if not in
remission:
- Eligible patients with aggressive histology (such as, but not limited to,
diffuse large B-cell NHL, mantle cell NHL, and T-cell histology) in CR by
PET/CT imaging.
- Eligible patients with indolent B-cell NHL (such as, but not limited to,
follicular, small cell or marginal zone NHL) will have 2nd or subsequent
progression with PR or CR by PET/CT imaging.
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN) in morphologic remission.
- Only for adult patients, to prevent graft rejection, patients who received only
non-lymphodepleting agents for their malignancy (hypomethylating agents, venetoclax,
hydroxyurea, TKIs etc.), or patients who received lymphodepleting chemotherapy > 3
months prior to scheduled admission, may receive fludarabine 25 mg/m^2 daily x 3
days for lymphodepletion 14-42 days (aiming for 2-4 weeks) at the discretion of the
principal investigator (PI).
- For patients > 18 years old, Karnofsky score ≥ 70%. For patients =< 18 years old,
Lansky score ≥ 50%.
- Calculated creatinine clearance > 70 ml/min.
- Bilirubin < 1.5 mg/dL (unless benign congenital hyperbilirubinemia or hemolysis).
- Alanine transaminase (ALT) < 3 x upper limit of normal (ULN).
- For patients > 18 years old, pulmonary function (spirometry and corrected diffusing
capacity for carbon monoxide [DLCO]) > 60% predicted. For patients =< 18 years old,
or any patient unable to perform pulmonary function tests, O2 saturation > 92% on
room air.
- Left ventricular ejection fraction > 50%.
- Albumin > 3.0 g/dL.
- For patients > 18 years old, Hematopoietic Cell Transplantation Comorbidity index
(HCT-CI) =< 5.
- UCB units will be selected according to current umbilical cord blood graft selection
algorithm. One or two UCB units may be used to achieve the required cell dose.
- The UCB graft is matched at 4-6 HLA-A, B, DRB1 antigens with the recipient. This may
include 0-2 antigen mismatches at the A or B or DRB1 loci. Unit selection based on
cryopreserved nucleated cell dose and HLA-A, B, DRB1 using intermediate resolution
A, B antigen and DRB1 allele typing.
Exclusion Criteria:
- Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow
fibrosis.
- Patients persistent with central nervous system (CNS) involvement in cerebrospinal
fluid (CSF) or CNS imaging at time of screening0
- Prior checkpoint inhibitors/ blockade in the last 12 months.
- Two prior stem cell transplants of any kind.
- One prior autologous stem cell transplant within the preceding 12 months.
- Prior allogeneic transplantation.
- Prior involved field radiation therapy that would preclude safe delivery of 400cGy
total body irradiation (TBI) in the opinion of radiation oncology.
- Active and uncontrolled infection at time of transplantation.
- HIV infection.
- Inadequate performance status/ organ function.
- Pregnancy or breast feeding.
- Patient or guardian unable to give informed consent or unable to comply with the
treatment protocol including appropriate supportive care, long-term follow-up, and
research tests.
Gender:
All
Minimum age:
6 Months
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutch/University of Washington Cancer Consortium
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ann Dahlberg
Phone:
206-667-1959
Email:
adahlber@fredhutch.org
Investigator:
Last name:
Ann Dahlberg
Email:
Principal Investigator
Start date:
July 23, 2024
Completion date:
October 31, 2032
Lead sponsor:
Agency:
Fred Hutchinson Cancer Center
Agency class:
Other
Collaborator:
Agency:
National Cord Blood Network
Agency class:
Other
Source:
Fred Hutchinson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06013423
