Study of Four Different Chemotherapy Regimens With or Without Total-Body Irradiation Followed by Umbilical Cord Blood Transplant in Treating Patients With Relapsed or Refractory Hematologic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00547196
First received: October 19, 2007
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

RATIONALE: Giving chemotherapy with or without total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the 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 before and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well four different chemotherapy regimens given with or without total-body irradiation before umbilical cord blood transplant work in treating patients with relapsed or refractory hematologic cancer.


Condition Intervention
Leukemia
Lymphoma
Myelodysplastic Syndromes
Biological: filgrastim
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: melphalan
Drug: mycophenolate mofetil
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: umbilical cord blood transplantation
Radiation: total-body irradiation

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation for Patients With Hematological Malignancies Using Multiple Unrelated Cord Blood Units

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Survival at day 100 after allogeneic hematopoietic stem cell transplantation (HSCT) from umbilical cord blood (UCB) [ Time Frame: Day 100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and timing of neutrophil engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Incidence and timing of platelet engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Incidence and severity of acute and chronic graft-versus-host-disease [ Time Frame: Up to 13 years ] [ Designated as safety issue: No ]
  • Survival at day 180 after HSCT from UCB transplantation [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Time from day 0 of transplantation to the first observation of relapse or death due to any cause, assessed up to 13 years ] [ Designated as safety issue: No ]
  • Incidence of primary and secondary engraftment failure [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Incidence of transplantation-related complications (e.g., infection, veno-occlusive disease of the liver, or organ toxicity) [ Time Frame: Up to 13 years ] [ Designated as safety issue: Yes ]
  • Incidence of post-transplantation-related lymphoproliferative disease, secondary myelodysplastic syndromes, and other secondary malignancies [ Time Frame: Up to 13 years ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Time Frame: Time from day 0 of transplantation to the first observation of relapse or death due to disease, assessed up to 13 years ] [ Designated as safety issue: No ]
  • Post-transplantation chimerism [ Time Frame: Up to 13 years ] [ Designated as safety issue: No ]
  • Immune reconstitution [ Time Frame: Up to 13 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: August 2003
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen I (age < 50 years, no contraindication to FTBI)
Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation Radiation: total-body irradiation
Experimental: Regimen II (age < 50 and unable to tolerate FTBI)
Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim Drug: busulfan Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Drug: mycophenolate mofetil Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation
Experimental: Regimen III (unable to tolerate regimen I or II)
Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation Radiation: total-body irradiation
Experimental: Regimen IV (unable to tolerate regimen I or II)
Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Drug: mycophenolate mofetil Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed hematological or lymphatic malignancy, including any of the following:

    • Acute myeloid leukemia

      • Relapsed or primary refractory disease with < 10% blasts on peripheral blood smear
      • In first remission with poor risk factors and molecular prognosis [i.e., AML with -5, -7, t(6;9), tri8, -11] (preparative regimen 3 or 4)
    • Acute lymphocytic leukemia

      • In second complete remission or higher OR in first remission with poor risk factors, including any of the following (preparative regimen 1 or 2):

        • BCR/ABL by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction
        • t(9;22)(q34;q11) detected by cytogenetics
        • Chromosomes < 44 by cytogenetics
        • DNA index < 0.81 by flow cytometry
        • Any rearrangement of chromosome 11 that results in disruption of MLL gene (11q23) by cytogenetics and SER
      • In first remission with poor risk factors and molecular prognosis [ALL with Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)] (preparative regimen 3 or 4)
    • Chronic myelogenous leukemia

      • In accelerated phase or greater (preparative regimen 1 or 2)
      • In accelerated or second chronic phase (preparative regimen 3 or 4)
    • Myelodysplastic syndromes

      • With deletion of chromosome 7 or short arm of chromosome 5 (preparative regimen 1 or 2)
      • In high and high-intermediate risk categories (preparative regimen 3 or 4)
    • Non-Hodgkin lymphoma in relapse with marrow involvement
    • Refractory chronic lymphocytic leukemia
  • Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e., regimens 1 or 2) due to any of the following concurrent medical conditions may be eligible for regimens 3 or 4 at the discretion of the treating physician and principal investigator (preparative regimen 3 or 4):

    • LVEF < 50% and > 40%
    • FEV1, FVC, or DLCO < 50%
    • Bilirubin > 3 mg/dL
    • Creatinine > 2 mg/dL
  • Two partially HLA-matched umbilical cord blood (UCB) units available

    • HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient

      • DRB1 matched by high resolution DNA typing
      • HLA-A and HLA-B matched by low resolution at the "serological match" level
    • Two pooled units with a nucleated cell number > 2.5 x 10^7/kg
  • No available HLA-identical sibling or 1 antigen-mismatched related donor
  • No available HLA-matched unrelated bone marrow donor

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1
  • Physiological age 60 or less (at any chronological age)
  • Weight > 50 kg
  • Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate > 60 mL/min
  • Bilirubin ≤ 1.5 mg/dL
  • LVEF ≥ 50%
  • DLCO ≥ 60% of predicted
  • No HIV-1 infection
  • No active uncontrolled infection
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • Recovered from prior intensive chemotherapy
  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: NCT00547196

Locations
United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Joseph Rosenthal, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00547196     History of Changes
Other Study ID Numbers: 02165, P30CA033572, CHNMC-02165, CDR0000570249
Study First Received: October 19, 2007
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
refractory chronic lymphocytic leukemia
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute lymphoblastic leukemia in remission
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Busulfan
Cyclophosphamide
Cyclosporine
Cyclosporins
Fludarabine
Fludarabine phosphate
Melphalan
Mycophenolate mofetil
Mycophenolic Acid
Vidarabine
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on October 23, 2014