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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00719888
First received: July 19, 2008
Last updated: May 11, 2015
Last verified: May 2015
  Purpose

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide (CY), fludarabine phosphate (FLU), and total-body irradiation (TBI) works in treating patients with hematologic disease. Giving chemotherapy, such as CY and FLU, 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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia in Remission
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Adult Acute Myeloid Leukemia in Remission
Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1
Aggressive Non-Hodgkin Lymphoma
B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1)
Burkitt Lymphoma
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Lymphoblastic Lymphoma
Mantle Cell Lymphoma
Myelofibrosis
Pancytopenia
Plasma Cell Myeloma
Prolymphocytic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Chronic Lymphocytic Leukemia
Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Recurrent Follicular Lymphoma
Recurrent Lymphoplasmacytic Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Anemia With Excess Blasts
Drug: Cyclophosphamide
Drug: Cyclosporine
Procedure: Double-Unit Umbilical Cord Blood Transplantation
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Radiation: Total-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A non-statistical comparison with historical controls will be made. Monitoring will take place separately for the single and double UCBT cohorts.


Secondary Outcome Measures:
  • Chimerism analysis [ Time Frame: Assessed up to 2 years ] [ Designated as safety issue: No ]
    Monitoring will take place separately for the single and double UCBT cohorts. Chimerism studies from peripheral blood and bone marrow samples will be sorted for CD3, CD14, CD33, and CD56 cells.

  • Incidence of chronic GVHD [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.

  • Incidence of clinically significant infections [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Monitoring will take place separately for the single and double UCBT cohorts.

  • Incidence of grade II-IV and III-IV acute GVHD [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
    Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. Monitoring will take place separately for the single and double UCBT cohorts.

  • Incidence of neutrophil engraftment [ Time Frame: At day 42 ] [ Designated as safety issue: No ]
    Monitoring will take place separately for the single and double UCBT cohorts.

  • Incidence of platelet recovery [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    Monitoring will take place separately for the single and double UCBT cohorts.

  • Incidence of relapse [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Cumulative incidence estimates will be used to summarize the time-to-event outcomes.

  • Incidence of transplant-related mortality [ Time Frame: At 6 months ] [ Designated as safety issue: Yes ]
    Monitoring will take place separately for the single and double UCBT cohorts.

  • Progression-free survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    A non-statistical comparison with historical controls will be made. Cumulative incidence estimates will be used to summarize the time-to-event outcomes. Monitoring will take place separately for the single and double UCBT cohorts.


Estimated Enrollment: 75
Study Start Date: November 2005
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (myeloablative UCBT)

Patients receive myeloablative conditioning comprising FLU IV over 30 minutes on days -8 to -6, CY IV on days -7 and -6, and undergo TBI twice daily 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 -3 to 5 and then mycophenolate mofetil PO (if tolerated) on days 6-30. Mycophenolate mofetil is discontinued on day 30 or 7 days after engraftment if there is no acute GVHD.

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Cyclosporine
Given IV and PO
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • CYCLOSPORINE
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
Procedure: Double-Unit Umbilical Cord Blood Transplantation
Undergo double-unit UCBT
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • FLUDARABINE PHOSPHATE
  • Oforta
  • SH T 586
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mycophenolate Mofetil
Given IV and PO
Other Names:
  • Cellcept
  • MMF
  • MYCOPHENOLATE MOFETIL
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • TOTAL BODY IRRADIATION
  • total-body irradiation
  • Whole-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Undergo UCBT
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
  • umbilical cord blood transplantation

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the one year survival of patients undergoing umbilical cord blood transplantation (UCBT) after a myeloablative preparative regimen consisting of cyclophosphamide (CY), fludarabine (FLU), and fractionated total body irradiation (TBI).

SECONDARY OBJECTIVES:

I. Incidence of transplant-related mortality (TRM) at 6 months.

II. Chimerism at multiple time points.

III. Incidence of neutrophil engraftment at day 42.

IV. Incidence of platelet engraftment 6 months.

V. Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100.

VI. Incidence of chronic GVHD at day 100, 1 year and 2 years.

VII. Incidence of clinically significant infections at 6 months, 1 year and 2 years.

VIII. Incidence of disease free survival at 1 and 2 years.

IX. Incidence of relapse at 1 and 2 years.

OUTLINE:

Patients receive myeloablative conditioning comprising FLU intravenously (IV) over 30 minutes on days -8 to -6, CY IV on days -7 and -6, and undergo TBI twice daily 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 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 -3 to 5 and then mycophenolate mofetil PO (if tolerated) on days 6-30. Mycophenolate mofetil is discontinued on day 30 or 7 days after engraftment if there is no acute GVHD.

After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.

  Eligibility

Ages Eligible for Study:   6 Months to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • Acute myeloid leukemia:

    • High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7), or high risk (HR) as defined by referring institution treatment protocol, >= 2 cycles to obtain complete response (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2)
    • All patients must be in 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 in which 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, Colleen Delaney prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with principal investigator (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:

    • High risk CR1 [for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed lineage leukemia (MLL) rearrangements, hypodiploid]
    • Greater than 1 cycle to obtain CR; >= CR2
    • 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 in which 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, Colleen Delaney 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 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
  • 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)
  • Prior myeloablative transplant containing full dose TBI (greater than 8 Gray [Gy])
  • Any prior myeloablative transplant within the last 6 months
  • Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar), as part of their salvage therapy are not eligible for myeloablative umbilical cord blood transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00719888

Locations
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion Completed
Aurora, Colorado, United States, 80045
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Colleen Delaney    206-667-1385      
Principal Investigator: Colleen Delaney         
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98101
Contact: Thomas R. Chauncey    206-764-2199      
Principal Investigator: Thomas R. Chauncey         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Colleen Delaney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00719888     History of Changes
Other Study ID Numbers: 2010.00, NCI-2010-00190, FHCRC 2010.00, Protocol 2010, 2010.00, P30CA015704
Study First Received: July 19, 2008
Last Updated: May 11, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Burkitt Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic-Phase
Leukemia, Prolymphocytic
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Pancytopenia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Primary Myelofibrosis
Waldenstrom Macroglobulinemia
Anemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
DNA Virus Infections
Epstein-Barr Virus Infections

ClinicalTrials.gov processed this record on June 02, 2015