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

March 4, 2025 updated by: Ann Dahlberg, Fred Hutchinson Cancer Center

Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation or Cyclophosphamide/Fludarabine/Thiotepa/Total Body Irradiation Myeloablative Preparative Regimen

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients 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 single- or double-unit UCBT on day 0.

ARM II: 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 once daily (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 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 6 months, 1 year, and 2 years.

Study Type

Interventional

Enrollment (Actual)

135

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University Of Colorado Hospital
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium
      • Seattle, Washington, United States, 98101
        • VA Puget Sound Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 45 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate
  • Advanced myelofibrosis
  • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
  • Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma (NHL) after initial therapy if stage III/IV in first partial response (PR1) or after progression if stage I/II < 1 year; stage III/IV patients are eligible after progression in CR/PR
  • Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have progressed after at least two different prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant; these patients must be presented at primary care center (PCC) prior to enrollment, given potential competing eligibility on autotransplant protocols
  • Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >= CR1 or >= PR1

  • Large cell NHL > CR2/> second partial response (PR2):

    • Patients in CR2/PR2 with initial short remission (< 6 months) are eligible
    • These patients must be presented at PCC prior to enrollment, given potential competing eligibility on autotransplant protocols
  • Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
  • Performance status score: Karnofsky (for adults) >= 70% or Eastern Cooperative Oncology Group (ECOG) 0-1 or Lansky (for children) >= 50%
  • Creatinine < 2.0 mg/dL (for adults) or creatinine clearance > 60 ml/min (for children)
  • Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
  • Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal or a pediatric patient who is unable to perform pulmonary function tests (PFTs) but has adequate pulmonary function
  • Left ventricular ejection fraction > 45% or shortening fraction > 26%

Exclusion Criteria:

  • 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)
  • Patients with history of prior myeloablative transplant containing full dose TBI (greater than 8 gray [Gy]) will not be eligible for Regimen A; however, they may still enroll on Regimen B if they otherwise meet inclusion and exclusion criteria
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (myeloablative UCBT)

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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Fludarabine
Given IV
Other Names:
  • 118218
  • Fluorovidarabine
Drug: Cyclosporine
Given IV and PO
Other Names:
  • 27-400
  • Sandimmune
  • Ciclosporin
  • CsA
  • Neoral
  • Gengraf
  • Sandimmun
  • Cyclosporin
  • Cyclosporin A
  • OL 27-400
  • SangCya
Procedure: Double-Unit Umbilical Cord Blood Transplantation
Undergo double-unit UCBT
Drug: Mycophenolate Mofetil
Given IV and PO
Other Names:
  • Cellcept
  • MMF
Radiation: Total-Body Irradiation
Undergo high-dose or moderate-intensity TBI
Other Names:
  • Total Body Irradiation
  • TBI
  • SCT_TBI
  • Whole-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Undergo UCBT
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
Experimental: Arm II (myeloablative UCBT)

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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Fludarabine
Given IV
Other Names:
  • 118218
  • Fluorovidarabine
Drug: Thiotepa
Given IV
Other Names:
  • Girostan
  • Triethylene Thiophosphoramide
  • Triethylenethiophosphoramide
  • 1,1',1"-phosphinothioylidynetrisaziridine
  • 1,1',1''-Phosphinothioyldynetrisaziridine
  • 52-24-4
  • 6396
Drug: Cyclosporine
Given IV and PO
Other Names:
  • 27-400
  • Sandimmune
  • Ciclosporin
  • CsA
  • Neoral
  • Gengraf
  • Sandimmun
  • Cyclosporin
  • Cyclosporin A
  • OL 27-400
  • SangCya
Procedure: Double-Unit Umbilical Cord Blood Transplantation
Undergo double-unit UCBT
Drug: Mycophenolate Mofetil
Given IV and PO
Other Names:
  • Cellcept
  • MMF
Radiation: Total-Body Irradiation
Undergo high-dose or moderate-intensity TBI
Other Names:
  • Total Body Irradiation
  • TBI
  • SCT_TBI
  • Whole-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Undergo UCBT
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 1 year post-transplant
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Level of Chimerism at Multiple Time Points
Time Frame: Baseline up to 2 years post-transplant
Peripheral blood chimerism studies (sorted for CD3, CD14, CD33, CD56 cells) were collected for all UCBT recipients for days 28, 56, 80, 365, and 730 post-transplant. The combined median of the percent donor, along with full range, is captured to show change in level of chimerism at multiple time points up to 2 years post-transplant. Monitoring will take place separately for the single and double UCBT cohorts.
Baseline up to 2 years post-transplant
Incidence of Transplant-related Mortality (TRM)
Time Frame: At 6 months post-transplant
Defined as death due to complication (other than relapse) within 6 months following UCBT. Monitoring will take place separately for the single and double UCBT cohorts.
At 6 months post-transplant
Neutrophil Engraftment
Time Frame: Up to day 42 post-transplant
Neutrophil engraftment after UCBT is defined as the first day of absolute neutrophil count (ANC) ≥ 5 x 10⁸/L for 3 consecutive measures. Monitoring will take place separately for the single and double UCBT cohorts.
Up to day 42 post-transplant
Platelet Engraftment
Time Frame: Up to 6 months post-transplant
Platelet (PLT) engraftment after UCBT is defined as the first day of platelet count > 20,000/μl without subsequent transfusions for 7 days. Monitoring will take place separately for the single and double UCBT cohorts.
Up to 6 months post-transplant
Event of Grade II-IV and III-IV Acute Graft-versus-host Disease (aGVHD)
Time Frame: Up to day 100 post-transplant
Each event of aGVHD will be assigned an overall aGVHD score based on extent of skin rash, volume of diarrhea, and maximum bilirubin level, per protocol Appendix I, "GVHD Staging and Grading." Scores reported range from most mild at 2, to worse at 4. Monitoring will take place separately for the single and double UCBT cohorts.
Up to day 100 post-transplant
Event of Chronic Graft-verses-host-disease (cGVHD)
Time Frame: Up to 2 years post-transplant
Each event of cGVHD level will be assessed overall as either 'Limited' (mild and with single organ involvement) or 'Extensive' (involvement of two or more organs with symptoms) based on extent of skin rash, volume of diarrhea, and maximum bilirubin level, per protocol Appendix I, "GVHD Staging and Grading." Monitoring will take place separately for the single and double UCBT cohorts.
Up to 2 years post-transplant
Event of Clinically Significant Infections
Time Frame: Up to 2 years post-transplant
Each event of infection will be assessed to determine whether or not it is clinically significant. An infection is defined as clinically significant when it is scored as ≥ grade 3 (where worse outcomes are associated with higher grading) in accordance with the CTCAE version 3.0/protocol Appendix VI, and constitutes a Serious Adverse Event (SAE). Monitoring will take place separately for the single and double UCBT cohorts.
Up to 2 years post-transplant
Incidence of Relapse
Time Frame: At 1 and 2 years post-transplant
Relapse is defined as post-transplant disease recurrence in participants who had initially recovered or improved, with incidence measured from Day 0 to 1 year post-transplant, and from 1 year post-transplant to 2 years post-transplant. Monitoring will take place separately for the single and double UCBT cohorts.
At 1 and 2 years post-transplant
Progression-free Survival (PFS)
Time Frame: Up to 2 years post-transplant
PFS is defined as the time (in days) from UCBT until the disease progresses or the patient dies from any cause, with incidence measured up to 2 years post-transplant. Monitoring will take place separately for the single and double UCBT cohorts. Measure will be reported as the median amount of days from full minimum and maximum range.
Up to 2 years post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Investigators

  • Principal Investigator: Ann E. Dahlberg, Fred Hutch/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 18, 2005

Primary Completion (Actual)

December 22, 2023

Study Completion (Actual)

December 19, 2024

Study Registration Dates

First Submitted

July 19, 2008

First Submitted That Met QC Criteria

July 19, 2008

First Posted (Estimated)

July 22, 2008

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 4, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010.00
  • 2010 (Fred Hutch/University of Washington Cancer Consortium)
  • NCI-2010-00190 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RG2807002 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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