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Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer

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ClinicalTrials.gov Identifier: NCT00255710
Recruitment Status : Completed
First Posted : November 21, 2005
Last Update Posted : March 17, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE November 18, 2005
First Posted Date  ICMJE November 21, 2005
Last Update Posted Date March 17, 2010
Study Start Date  ICMJE July 2002
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
  • Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
  • Incidence and severity of acute GVHD at day 60 following transplant
  • Frequency of mixed chimerism defined as any detectable donor cells at day 60 following transplant
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00255710 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer
Official Title  ICMJE Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression
Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after transplant may stop this from happening.

PURPOSE: This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus to see which is the best regimen in treating patients who are undergoing a donor bone marrow or stem cell transplant for hematologic cancer.

Detailed Description

OBJECTIVES:

  • Determine a minimal (short-duration) post-transplant immunosuppression regimen comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-identical related donor.
  • Determine the post-transplant immunosuppression regimen that results in < 10% incidence of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in these patients.
  • Determine the incidence and severity of acute GVHD in patients treated with these regimens.
  • Determine the frequency of mixed chimerism in patients treated with these regimens.

OUTLINE:

  • Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF) beginning on day 5 and continuing until at least day 15 or until blood counts recover.
  • Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients are enrolled into 1 of the following regimens:

    • Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day 3 only.
    • Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil (MMF) once on day 3 and then twice daily on days 4-32.
    • Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on days 3 and 4 and MMF twice daily on days 4-33.
    • Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3.
    • Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3 and tacrolimus twice daily on days 4-33.

Cohorts of approximately 10-20 patients receive sequentially increasing levels of post-transplant immunosuppression until a minimal (short-duration) post-transplant immunosuppression regimen is identified. The minimal post-transplant immunosuppression regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is identified, an additional 10 patients are treated with that regimen.

Patients are followed for 60 days after transplantation.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
Intervention  ICMJE
  • Biological: filgrastim
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
  • Drug: tacrolimus
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: radiation therapy
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
60
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:

    • Stage II or III multiple myeloma
    • Amyloidosis
    • Myelofibrosis with ≥ 2 of the following high-risk features:

      • Over 55 years of age
      • Hemoglobin < 10 g/dL
      • WBC < 3,000/mm^3 OR > 10,000/mm^3
      • Platelet count < 100,000/mm^3
      • Cytogenetic abnormalities
    • Mycosis fungoides, meeting 1 of the following criteria:

      • Stage IIB or III disease with evidence of histologic conversion to an aggressive lymphoma

        • Must demonstrate chemosensitivity
      • Stage IV disease
    • Paroxysmal nocturnal hemoglobinuria

      • Not meeting criteria for other bone marrow transplantation (BMT) or treatment studies
    • Diagnosis of 1 of the following hematologic malignancies, for which patient is not eligible for potentially curative allogeneic BMT due to end-organ dysfunction, age 65 to 75, or the amount of prior chemotherapy:

      • Acute myeloid or acute lymphoblastic leukemia

        • High-risk disease in first or second (or further) complete remission
      • Relapsed aggressive non-Hodgkin's lymphoma

        • Not eligible for autologous or standard allogeneic BMT
      • Hodgkin's lymphoma in second or further complete or partial remission

        • Not eligible for autologous or standard allogeneic BMT
      • Myelodysplastic syndromes or myelodysplastic/myeloproliferative diseases

        • Any of the following subtypes:

          • Refractory anemia with excess blasts (RAEB)
          • RAEB in transformation
          • Chronic myelomonocytic leukemia
          • Any morphologic subtype with multiple chromosomal abnormalities
          • Any subset with life-threatening cytopenias in all 3 cell lines, defined as platelet count ≤ 20,000/mm^3, absolute neutrophil count ≤ 500/mm^3, and reticulocyte count ≤ 50,000/mm^3
        • Meets both of the following criteria:

          • Less than 20% blasts by bone marrow biopsy
          • Not eligible for standard allogeneic BMT
        • No refractory anemia with ringed sideroblasts
        • No 5q syndrome
      • Stage III or IV chronic lymphocytic leukemia

        • Not meeting criteria for other BMT studies
      • Chronic myelogenous leukemia in first or second chronic phase

        • Not meeting criteria for other BMT studies or treatment
      • Stage III or IV indolent small lymphocytic or follicular lymphoma

        • Not eligible for autologous or standard allogeneic BMT or other active protocols at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Must have an HLA-identical related donor available

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 3.0 mg/dL
  • AST ≤ 175 U/L
  • ALT ≤ 200 U/L

Renal

  • Creatinine ≤ 3.0 mg/dL

Cardiovascular

  • LVEF ≥ 30%

Pulmonary

  • FEV_1 ≥ 40% predicted
  • Forced vital capacity ≥ 40% predicted

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

PRIOR CONCURRENT THERAPY:

Chemotherapy

  • See Disease Characteristics
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00255710
Other Study ID Numbers  ICMJE CDR0000449652
P01CA015396 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0169
WIRB-20020304
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Carol A. Huff, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date March 2010

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