Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 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: May 10, 2016
Last verified: May 2016

July 25, 2008
May 10, 2016
June 2008
September 2017   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
Kaplan-Meier and cumulative incidence estimates will be used.
  • Survival at 1 year [ Designated as safety issue: No ]
  • Engraftment rates [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00723099 on ClinicalTrials.gov Archive Site
  • 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
  • Overall survival (i.e., beyond 1 year) [ Designated as safety issue: No ]
  • Nonrelapse mortality at 6 months, 1 year, and overall [ Designated as safety issue: No ]
  • Incidence of graft failure/rejection [ Designated as safety issue: Yes ]
  • Neutrophil and platelet engraftment [ Designated as safety issue: Yes ]
  • Acute and chronic GVHD [ Designated as safety issue: Yes ]
  • Relapse [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Clinically significant infections [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Reduced-Intensity Preparative Regimen
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.

PRIMARY OBJECTIVES:

I. Estimate probability of one year survival.

II. For Arm 2: Demonstrate equivalent or improved engraftment rates with a non-anti-thymocyte globulin (ATG) based conditioning regimen. Patients will be considered graft failure/rejections provided they meet any of the criteria listed below:

  • Absence of 3 consecutive days with neutrophils >= 500/ul combined with host cluster of differentiation (CD)3 peripheral blood chimerism >= 50% at day 42
  • Absence of 3 consecutive days with neutrophils >= 500/ul under any circumstances at day 55
  • Death after day 28 with neutrophil count < 100/ul without any evidence of engraftment (< 5% donor CD3)
  • Primary autologous count recovery with < 5% donor CD3 peripheral blood chimerism at count recovery and without relapse

SECONDARY OBJECTIVES:

I. Six month non-relapse mortality.

II. Overall incidence of graft failure/rejection. Patients will be considered graft failure/rejections provided they meet any of the criteria listed below:

  • Absence of 3 consecutive days with neutrophils >= 500/ul combined with host CD3 peripheral blood chimerism >= 50% at day 42
  • Absence of 3 consecutive days with neutrophils >= 500/ul under any circumstances at day 55
  • Death after day 28 with neutrophil count < 100/ul without any evidence of engraftment (< 5% donor CD3)
  • Primary autologous count recovery with < 5% donor CD3 peripheral blood chimerism at count recovery and without relapse

III. Kinetics of chimeric reconstitution.

IV. Incidence of neutrophil engraftment by day 42.

V. Incidence of platelet engraftment by six months.

VI. Incidence of grade II-IV and III-IV acute graft-versus-host disease (GvHD) for each arm at day 100.

VII. Incidence of one year chronic GvHD for each arm.

VIII. Incidence of clinically significant infections at 6 months, 1 year, 2 years for each arm.

IX. Probability of one and two year survival.

X. Incidence of one and two year relapse or disease progression.

XI. Fred Hutchinson Cancer Research Center (FHCRC) patients: Kinetics of immune reconstitution, with both functional and quantitative assays.

XII. FHCRC patients: Examination of possible immunologic factors leading to emergence of a dominant unit.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (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 total-body irradiation (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 -3 to +180 and mycophenolate mofetil IV or orally (PO) every 8 hours on days 0 to +96.

ARM II:

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.

After completion of study treatment, patients are followed periodically for up to 2 years.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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 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.

    Interventions:
    • 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
  • 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.

    Interventions:
    • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
85
Not Provided
September 2017   (final data collection date for primary outcome measure)

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
Both
up to 69 Years   (Child, Adult, Senior)
No
United States
 
NCT00723099
2239.00, NCI-2009-01551, 2239, 2239.00, P30CA015704
Yes
Not Provided
Not Provided
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Rachel Salit Fred Hutch/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP