Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases

NCT ID: NCT06013423

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-23
• Study Completion Date: 2032-10-31

Brief 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 throughout the study 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 throughout the study and bone marrow aspirate during screening and on study.

All 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.

Conditions

Acute Leukemia of Ambiguous Lineage; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Hematopoietic and Lymphatic System Neoplasm; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Chronic Myeloid Leukemia, BCR-ABL1 Positive

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (myeloablative UCBT)

See detailed description.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Bone Marrow Aspirate

Intervention Type: PROCEDURE

Undergo bone marrow aspirate

Cyclophosphamide

Intervention Type: DRUG

Receive IV

Cyclosporine

Intervention Type: DRUG

Receive IV or PO

Diagnostic Imaging

Intervention Type: PROCEDURE

Undergo diagnostic imaging

Echocardiography

Intervention Type: PROCEDURE

Undergo ECHO

Fludarabine Phosphate

Intervention Type: DRUG

Receive IV

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA

Mycophenolate Mofetil

Intervention Type: DRUG

Receive IV

Survey Administration

Intervention Type: OTHER

Ancillary studies

Total-Body Irradiation

Intervention Type: RADIATION

Undergo high-dose or middle-intensity TBI

Umbilical Cord Blood Transplantation

Intervention Type: PROCEDURE

Undergo UCBT

Arm II (myeloablative UCBT)

See detailed description.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Bone Marrow Aspirate

Intervention Type: PROCEDURE

Undergo bone marrow aspirate

Cyclophosphamide

Intervention Type: DRUG

Receive IV

Cyclosporine

Intervention Type: DRUG

Receive IV or PO

Diagnostic Imaging

Intervention Type: PROCEDURE

Undergo diagnostic imaging

Echocardiography

Intervention Type: PROCEDURE

Undergo ECHO

Fludarabine Phosphate

Intervention Type: DRUG

Receive IV

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA

Mycophenolate Mofetil

Intervention Type: DRUG

Receive IV

Survey Administration

Intervention Type: OTHER

Ancillary studies

Thiotepa

Intervention Type: DRUG

Receive IV

Total-Body Irradiation

Intervention Type: RADIATION

Undergo high-dose or middle-intensity TBI

Umbilical Cord Blood Transplantation

Intervention Type: PROCEDURE

Undergo UCBT

Interventions

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Bone Marrow Aspirate

Undergo bone marrow aspirate

Intervention Type: PROCEDURE

Cyclophosphamide

Receive IV

Intervention Type: DRUG

Cyclosporine

Receive IV or PO

Intervention Type: DRUG

Diagnostic Imaging

Undergo diagnostic imaging

Intervention Type: PROCEDURE

Echocardiography

Undergo ECHO

Intervention Type: PROCEDURE

Fludarabine Phosphate

Receive IV

Intervention Type: DRUG

Multigated Acquisition Scan

Undergo MUGA

Intervention Type: PROCEDURE

Mycophenolate Mofetil

Receive IV

Intervention Type: DRUG

Survey Administration

Ancillary studies

Intervention Type: OTHER

Thiotepa

Receive IV

Intervention Type: DRUG

Total-Body Irradiation

Undergo high-dose or middle-intensity TBI

Intervention Type: RADIATION

Umbilical Cord Blood Transplantation

Undergo UCBT

Intervention Type: PROCEDURE

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; BONE MARROW, LIQUID; Human Bone Marrow Aspirate; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; 27-400; Ciclosporin; CsA; Cyclosporin; Cyclosporin A; Cyclosporine Modified; Gengraf; Neoral; OL 27-400; Sandimmune; SangCya; Medical Imaging; EC; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; Gated Heart Pool Scan; MUGA; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; CellCept; MMF; 1,1',1''-Phosphinothioylidynetrisaziridine; Girostan; N,N', N''-Triethylenethiophosphoramide; Oncotiotepa; STEPA; Tepadina; TESPA; Tespamin; Tespamine; Thio-Tepa; Thiofosfamide; Thiofozil; Thiophosphamide; Thiophosphoramide; Thiotef; Tifosyl; TIO TEF; Tio-tef; Triethylene Thiophosphoramide; Triethylenethiophosphoramide; Tris(1-aziridinyl)phosphine sulfide; TSPA; WR 45312; SH105; SCT_TBI; TBI; Total Body Irradiation; Whole Body; Whole Body Irradiation; Whole-Body Irradiation; Cord Blood; Cord Blood Transplantation; UCB transplantation; UMBILICAL CORD BLOOD TRANSPLANT

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cord Blood Network

UNKNOWN

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann Dahlberg

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ann Dahlberg

Role: CONTACT

adahlber@fredhutch.org

206-667-1959

Facility Contacts

Ann Dahlberg

Role: primary

adahlber@fredhutch.org

206-667-1959

Other Identifiers

NCI-2023-05598

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020219

Identifier Type: OTHER

Identifier Source: secondary_id

RG1123652

Identifier Type: -

Identifier Source: org_study_id