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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00255710
First received: November 18, 2005
Last updated: March 16, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
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
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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

Estimated Enrollment: 60
Study Start Date: July 2002
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00255710

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Carol A. Huff, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00255710     History of Changes
Other Study ID Numbers: CDR0000449652, P01CA015396, P30CA006973, JHOC-J0169, WIRB-20020304
Study First Received: November 18, 2005
Last Updated: March 16, 2010
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
graft versus host disease
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
adult acute myeloid leukemia in remission
chronic idiopathic myelofibrosis
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
previously treated myelodysplastic syndromes
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
stage II multiple myeloma
stage III adult Hodgkin lymphoma
stage III chronic lymphocytic leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III multiple myeloma
stage III small lymphocytic lymphoma
stage IV adult Hodgkin lymphoma
stage IV chronic lymphocytic leukemia
stage IV grade 1 follicular lymphoma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Lymphoma
Leukemia
Syndrome
Graft vs Host Disease
Plasmacytoma
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Disease
Pathologic Processes
Cyclophosphamide
Tacrolimus

ClinicalTrials.gov processed this record on September 18, 2014