Multiple Myeloma Clinical Trial
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
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.
Full 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 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
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There is 1 Location for this study
Baltimore Maryland, 21231, United States
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