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

NCT06013423 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1123652NCI-2023-05598FHIRB0020219
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

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; Acute Leukemia of Ambiguous Lineage; Chronic Myeloid Leukemia, BCR-ABL1 Positive

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Will be assessed after optimized cord blood transplant (CBT) in adults and children with hematologic malignancies. Will be calculated using the Kaplan-Meier method.

  At 1 year

Secondary Outcomes (12)

• Cumulative incidence of neutrophil and platelet engraftment

  Up to 1 year

• Incidences of graft failure

  Up to 1 year

• Incidence of grade II-IV and III-IV acute graft-versus-host disease (aGVHD)

  At day 100

• Incidence of grade II-IV and III-IV aGVHD

  At day 180

• Incidence of chronic graft-versus-host disease (cGVHD)

  At 1, 2 and 3 years

Study Arms (2)

Arm I (myeloablative UCBT)

EXPERIMENTAL

See detailed description.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspirate; Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Diagnostic Imaging; Procedure: Echocardiography; Drug: Fludarabine Phosphate; Procedure: Multigated Acquisition Scan; Drug: Mycophenolate Mofetil; Other: Survey Administration; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Arm II (myeloablative UCBT)

EXPERIMENTAL

See detailed description.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspirate; Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Diagnostic Imaging; Procedure: Echocardiography; Drug: Fludarabine Phosphate; Procedure: Multigated Acquisition Scan; Drug: Mycophenolate Mofetil; Other: Survey Administration; Drug: Thiotepa; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Bone Marrow Aspirate PROCEDURE

Undergo bone marrow aspirate

Also known as: BONE MARROW, LIQUID, Human Bone Marrow Aspirate

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Cyclophosphamide DRUG

Receive IV

Also known as: (-)-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

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Cyclosporine DRUG

Receive IV or PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Diagnostic Imaging PROCEDURE

Undergo diagnostic imaging

Also known as: Medical Imaging

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Fludarabine Phosphate DRUG

Receive IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: 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

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Mycophenolate Mofetil DRUG

Receive IV

Also known as: CellCept, MMF

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Survey Administration OTHER

Ancillary studies

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Thiotepa DRUG

Receive IV

Also known as: 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

Arm II (myeloablative UCBT)

Total-Body Irradiation RADIATION

Undergo high-dose or middle-intensity TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Umbilical Cord Blood Transplantation PROCEDURE

Undergo UCBT

Also known as: Cord Blood, Cord Blood Transplantation, UCB transplantation, UMBILICAL CORD BLOOD TRANSPLANT

Arm I (myeloablative UCBT); Arm II (myeloablative UCBT)

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cord Blood Network: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Blastic Plasmacytoid Dendritic Cell Neoplasm; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Specimen Handling; Fluid Therapy; Cyclophosphamide; Cyclosporine; Cyclosporins; X-Rays; fludarabine phosphate; Mycophenolic Acid; Thiotepa; Whole-Body Irradiation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Drug Therapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Study Officials

• Ann Dahlberg

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ann Dahlberg

CONTACT

206-667-1959; adahlber@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: August 28, 2023
• Study Start: July 23, 2024
• Primary Completion (Estimated): October 31, 2031
• Study Completion (Estimated): October 31, 2032
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)