Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00723099
First received: July 25, 2008
Last updated: November 13, 2015
Last verified: November 2015
  Purpose
This phase II trial is studying how well umbilical cord blood transplant from a donor works in treating patients with hematological cancer. Giving chemotherapy and total-body irradiation (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 an unrelated donor, that do not exactly match the patient's blood, 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 (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

Condition Intervention Phase
Acute Biphenotypic Leukemia
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Aggressive Non-Hodgkin Lymphoma
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Indolent Non-Hodgkin Lymphoma
Malignant Lymphoma, Large Cell Type
Mixed Phenotype Acute Leukemia
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Recurrent Chronic Lymphocytic Leukemia
Recurrent Follicular Lymphoma
Recurrent Lymphoplasmacytic Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Plasma Cell Myeloma
Recurrent Small Lymphocytic Lymphoma
Recurrent T-Cell Non-Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Refractory Follicular Lymphoma
Refractory Hodgkin Lymphoma
Refractory Lymphoplasmacytic Lymphoma
Refractory Mantle Cell Lymphoma
Refractory Small Lymphocytic Lymphoma
T-Cell Non-Hodgkin Lymphoma
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Cyclophosphamide
Drug: Cyclosporine
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: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Reduced-Intensity 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: At 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.


Secondary Outcome Measures:
  • Incidence of chronic GVHD for each arm [ Time Frame: At 1 year ] [ Designated as safety issue: Yes ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of clinically significant infections [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of grade II-IV and III-IV acute GVHD for each arm [ Time Frame: By day 100 ] [ Designated as safety issue: Yes ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of graft failure/rejection [ Time Frame: By day 55 ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of neutrophil engraftment [ Time Frame: By day 42 ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of non-relapse mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used

  • Incidence of non-relapse mortality [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of non-relapse mortality [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of platelet engraftment [ Time Frame: By 6 months ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Incidence of relapse or disease progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used.

  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used

  • Progression-free survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier and cumulative incidence estimates will be used


Estimated Enrollment: 85
Study Start Date: June 2008
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (lower dose of TBI)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients undergo a lower dose of TBI on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo umbilical cord blood transplant
Other Names:
  • allogeneic stem cell transplantation
  • HSC
  • HSCT
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
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Cyclosporine
Given IV
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
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
  • Oforta
  • SH T 586
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Undergo umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
Experimental: Arm II (higher dose of TBI)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate and cyclophosphamide as in Arm I. Patients undergo a higher dose of TBI on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion as in Arm I.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine and mycophenolate mofetil as in Arm I.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo umbilical cord blood transplant
Other Names:
  • allogeneic stem cell transplantation
  • HSC
  • HSCT
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
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Cyclosporine
Given IV
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
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
  • Oforta
  • SH T 586
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Undergo umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients > 70 may be considered if performance status > 80% or Eastern Cooperative Oncology Group (ECOG) < 1 and comorbidity score < 3
  • Adequate cardiac function defined as absence of decompensated congestive heart failure, or uncontrolled arrhythmia and:

    • Left ventricular ejection fraction >= 35% or
    • Fractional shortening > 22%
  • Adequate pulmonary function defined as diffusion capacity of carbon monoxide (DLCO) > 30% predicted, and absence of oxygen (O2) requirements
  • Adequate hepatic function; 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
  • Adequate renal function defined as creatinine =< 2.0 mg/dl (adults) or creatinine clearance > 40 ml/min (pediatrics)
  • All adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min
  • Performance status score: Karnofsky (for adults) >= 60 or ECOG 0-2; Lansky (for children) score >= 50
  • If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease
  • Second hematopoietic cell transplant: Must be >= 3 months after prior myeloablative transplant
  • Acute myeloid leukemia and acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia: Must have < 5% morphologic marrow blasts in an evaluable marrow (> 25% of normal cellularity for age) collected less than one month prior to start of conditioning; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with the approval of the principal investigator (PI) or designee
  • Chronic myelogenous leukemia: All types, except refractory blast crisis; chronic phase patients must have failed or been intolerant to Gleevec or other tyrosine kinase inhibitors; at time of transplant, patients must have < 5% blasts in an evaluable marrow (> 25% of normal cellularity for age) by morphology within the bone marrow
  • Myelodysplastic syndrome (MDS): Any subtype; morphologic blasts must be less than 5% in an evaluable marrow (> 25% of normal cellularity for age); if blasts are 5% or more, patient requires induction chemotherapy pre-transplant to reduce blast count to less than 5%; patients who have a hypocellular marrow in the absence of excess blasts that is related to the underlying disease or as a result of treatment for MDS may also be eligible with the approval of the PI or designee
  • Large-cell lymphoma and aggressive T-cell lymphoma: With chemotherapy sensitive disease that has failed autologous transplant or patients who are ineligible for an autologous transplant; chemotherapy sensitive disease is defined as >= 50% reduction in the size of the tumor with the chemotherapy regimen immediately preceding transplant
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory to fludarabine (fludarabine phosphate) or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
  • Hodgkin disease: Must have received and failed frontline therapy
  • Follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, and indolent T-cell lymphomas: Must have progressed with the most recent remission duration being < 6 months
  • Follicular lymphoma, marginal zone B-Cell lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, and indolent T-cell lymphomas: Patients with bulky disease should be considered for debulking chemotherapy before transplant; patients with refractory disease are eligible, unless they have bulky disease and an estimated tumor doubling time of less than one month
  • Multiple myeloma: Must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative hematopoietic cell transplant (HCT) is permitted
  • Myeloproliferative syndromes
  • DONOR: Cord blood (CB) donor selection will be based on institutional guidelines and in general should be selected to optimize both human leukocyte antigen (HLA) match and cell dose; additionally, CB grafts shall consist of one or two CB donors based on, but not exclusively determined by, cell dose (total nucleated cell [TNC]/kg and CD34/kg), HLA matching and disease status and indication for transplant; attending preference will be allowed for single versus double unit as well as the degree of mismatching based on patient specific factors, as long as the following minimum criteria are met:

    • HLA matching

      • Minimum requirement: The CB graft(s) must be matched at a minimum at 4/6 HLA-A, B, DRB1 loci with the recipient. Therefore 0-2 mismatches at the A or B or DRB1 loci based on intermediate resolution A, B antigen and DRB1 allele typing for determination of HLA-match is allowed
      • HLA-matching determined by high-resolution typing is allowed per institutional guidelines as long as the minimum criteria are met
    • Selection of two CB units is mandatory when a single cord blood unit does not meet the following criteria:

      • Match grade 6/6; TNC Dose >= 2.5 x 10^7/kg
      • Match grade 5/6 or 4/6; TNC dose >= 4.0 (+/- 0.5) x 10^7/kg
    • If two CB units are used, the total cell dose of the combined units must be at least 3.0 x 10^7 TNC per kilogram recipient weight based on pre-cryopreservation numbers, with each CB unit containing a MINIMUM of 1.5 x 10^7 TNC/kg
    • The minimum recommended CD34/kg cell dose should be 2 x 10^5 CD34/kg, total dose from a single or combined double
    • The unmanipulated CB unit(s) will be Food and Drug Administration (FDA) licensed or will be obtained under a separate investigational new drug (IND), such as the National Marrow Donor Program (NMDP) Protocol 10-CBA conducted under BB IND-7555 or another IND sponsored by (1) a participating institution or (2) an investigator at FHCRC or one of the participating institutions
    • FHCRC only: Up to 5% of cord blood product, when ready for infusion, may be withheld for research purposes as long as thresholds for infused TNC dose are met; threshold for double unit transplantation is >= 3.0 x 10^7/kg; these products will be used to conduct studies involving the immunobiology of double cord transplantation and kinetics of engraftment
  • DONOR: The patient and the cord blood unit(s) must be matched for at least 4 of 6 loci

Exclusion Criteria:

  • Patients with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
  • Pregnancy or breastfeeding
  • Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
  • Uncontrolled viral or bacterial infection at the time of study enrollment
  • Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
  • Active central nervous system malignancy
  • DONOR: Any cord blood units with < 1.5 x 10^7 total nucleated cells per kilogram recipient weight
  • DONOR: Any cord blood units without the full maternal testing and negative results for hepatitis A, B, C, HIV, and human T-lymphotropic virus (HTLV-1) viruses
  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: NCT00723099

Locations
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion Active, not recruiting
Aurora, Colorado, United States, 80045
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Juli Murphy    720-754-4890    Juli.Murphy@HealthONEcares.com   
Principal Investigator: Michael B. Maris         
United States, Utah
LDS Hospital Recruiting
Salt Lake City, Utah, United States, 84143
Contact: Finn B. Petersen    303-388-4876    finn.petersen@intermountainmail.org   
Principal Investigator: Finn B. Petersen         
United States, Washington
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98101
Contact: Thomas R. Chauncey    206-764-2709    tchaunce@u.washington.edu   
Principal Investigator: Thomas R. Chauncey         
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Rachel B. Salit    206-667-1317    rsalit@fredhutch.org   
Principal Investigator: Rachel B. Salit         
United States, Wisconsin
Froedtert and the Medical College of Wisconsin Completed
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Rachel Salit Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00723099     History of Changes
Other Study ID Numbers: 2239.00  NCI-2009-01551  2239  2239.00  P30CA015704 
Study First Received: July 25, 2008
Last Updated: November 13, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hodgkin Disease
Leukemia
Leukemia, Biphenotypic, Acute
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic-Phase
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Multiple Myeloma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 02, 2016