Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With Hematologic Disease

NCT00719888 | Completed Phase 2 Results DMC

• 4 other identifiers: 2010.00NCI-2010-001902010RG2807002
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 3

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 disease. Giving chemotherapy, such as cyclophosphamide and fludarabine, and TBI before a donor umbilical cord blood transplant 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.

Conditions

Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Burkitt Lymphoma; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Follicular Lymphoma; Lymphoblastic Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Refractory Anemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival defined as patient being alive at 1 year post-transplant. Monitoring will take place separately for the single and double UCBT cohorts.

  1 year post-transplant

Secondary Outcomes (9)

• Change in Level of Chimerism at Multiple Time Points

  Baseline up to 2 years post-transplant

• Incidence of Transplant-related Mortality (TRM)

  At 6 months post-transplant

• Neutrophil Engraftment

  Up to day 42 post-transplant

• Platelet Engraftment

  Up to 6 months post-transplant

• Event of Grade II-IV and III-IV Acute Graft-versus-host Disease (aGVHD)

  Up to day 100 post-transplant

Study Arms (2)

Treatment (myeloablative UCBT)

EXPERIMENTAL

Patients receive myeloablative conditioning comprising fludarabine IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI BID on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine 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) 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.

Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Double-Unit Umbilical Cord Blood Transplantation; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Arm II (myeloablative UCBT)

EXPERIMENTAL

Patients 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 QD on days -2 and -1. Patients then undergo single- or double-unit UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine 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) 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.

Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Double-Unit Umbilical Cord Blood Transplantation; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Drug: Thiotepa

Interventions

Cyclophosphamide DRUG

Given 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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Cyclosporine DRUG

Given IV and PO

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

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Double-Unit Umbilical Cord Blood Transplantation PROCEDURE

Undergo double-unit UCBT

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Fludarabine DRUG

Given IV

Also known as: 118218, Fluorovidarabine

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Mycophenolate Mofetil DRUG

Given IV and PO

Also known as: Cellcept, MMF

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Total-Body Irradiation RADIATION

Undergo high-dose or moderate-intensity TBI

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

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Umbilical Cord Blood Transplantation PROCEDURE

Undergo UCBT

Also known as: Cord Blood Transplantation, UCB transplantation

Arm II (myeloablative UCBT); Treatment (myeloablative UCBT)

Thiotepa DRUG

Given IV

Also known as: 1,1',1"-phosphinothioylidynetrisaziridine, 1,1',1''-Phosphinothioyldynetrisaziridine, 52-24-4, 6396, Girostan, Triethylenethiophosphoramide, Triethylene Thiophosphoramide

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:

• GRAFT CRITERIA:
• UCB units will be selected according to current umbilical cord blood graft selection algorithm; one or 2 UCB units may be used to achieve the required cell dose
• The UCB graft is matched at 4-6 human leukocyte antigen (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
• If 2 UCB units are required to reach the target cell dose, each unit must be a 4-6 antigen match to the recipient
• Age and Disease Criteria:
• High-dose TBI regimen: 6 months to =\< 45 years
• Middle-intensity TBI regimen: 6 months to =\< 65 years
• Conditioning regimen selection should be based on the underlying disease, presence of minimum residual disease (MRD), age, co-morbidities, and attending physician
• Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:
• All patients must be in complete remission (CR) as defined by hematologic recovery and \< 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity \>= 15% for age; patients who do not have high-risk features (for example preceding myelodysplastic syndrome \[MDS\], high-risk cytogenetics, \>= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia or \>= CR2) must be discussed with the principal investigator (PI) prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
• Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the PI prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
• Very high risk pediatric/young adult patients with acute myeloid leukemia (AML): Patients =\< 25 years, however, are eligible with (M2 marrow) with =\< 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately
• Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:
• All patients must be in CR as defined by \< 5% blasts by morphology; flow cytometry in a representative bone marrow sample with cellularity \>= 15% for age; patients who do not have high-risk disease (high risk CR1, greater than one cycle to obtain CR or \>= CR2) must be discussed with the PI prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
• Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator Ann Dahlberg prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval

You may not qualify if:

• Uncontrolled viral or bacterial infection at the time of study enrollment
• Active or recent (prior 6 month) invasive fungal infection without interdisciplinary (ID) consult and approval
• History of human immunodeficiency virus (HIV) infection
• Pregnant or breastfeeding
• Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after \> 2 salvage regimens)
• Any prior myeloablative transplant within the last 6 months
• Patients \>= 45 years: comorbidity score of 5 or higher
• Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy are not eligible for Regimen A

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (3)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Burkitt Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Myelodysplastic Syndromes; Primary Myelofibrosis; Lymphoma, Non-Hodgkin; Multiple Myeloma; Leukemia, Prolymphocytic; Anemia, Refractory

Interventions

Cyclophosphamide; Cyclosporine; Cyclosporins; fludarabine; Mycophenolic Acid; Whole-Body Irradiation; Cord Blood Stem Cell Transplantation; Thiotepa

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; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders; Bone Marrow Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Anemia

Intervention Hierarchy (Ancestors)

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; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Radiotherapy; Therapeutics; Investigative Techniques; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study initiated in 2005, but Arm B was added to the study design in 2019. Therefore patient accrual in Arm B is lower than Arm A, though rate of accrual was comparable once both arms were available.

Results Point of Contact

• Title: Dr. Ann Dahlberg
• Organization: Fred Hutchinson Cancer Center

adahlber@fredhutch.org

206-667-1959

Study Officials

• Ann E. Dahlberg

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 19, 2008
• First Posted: July 22, 2008
• Study Start: November 18, 2005
• Primary Completion: December 22, 2023
• Study Completion: December 19, 2024
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)