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

NCT ID: NCT00255710

Last Updated: 2010-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31

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.

Conditions

Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

mycophenolate mofetil

Intervention Type: DRUG

tacrolimus

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Principal Investigators

Carol A. Huff, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

P01CA015396

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0169

Identifier Type: -

Identifier Source: secondary_id

WIRB-20020304

Identifier Type: -

Identifier Source: secondary_id

CDR0000449652

Identifier Type: -

Identifier Source: org_study_id