RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Bone marrow transplantation may be able to replace immune cells that have been destroyed by radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Mycophenolate mofetil and tacrolimus may be an effective treatment for graft-versus-host disease caused by bone marrow transplantation. PURPOSE: Phase II trial to study the effectiveness of total-body irradiation, tacrolimus, and mycophenolate mofetil plus bone marrow transplantation in treating patients with hematologic cancers.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Multiple Myeloma	Drug: mycophenolate mofetil  Drug: tacrolimus	Phase II

Further Study Details: 

OBJECTIVES: I. Determine whether sustained engraftment of HLA identical sibling marrow can be achieved in patients treated with total body irradiation before transplant and tacrolimus and mycophenolate mofetil after transplant. II. Document the nonhematologic toxicities of this regimen. III. Characterize immune reconstitution of patients during this treatment regimen. IV. Document the incidence of aplasia and graft-versus-host disease associated with donor leukocyte infusions when administered after this regimen.

PROTOCOL OUTLINE: Patients receive total body irradiation in a single fraction on day -1. Tacrolimus is given orally twice per day on days -1 to 50. Mycophenolate mofetil is given orally on day 0 and twice per day on days 1 to 28. Patients receive donor bone marrow infusion on day 0. Patients are evaluated on days 56, 180, 292, and 365. If there is donor engraftment, donor chimerism is less than 80%, there is no active graft-versus-host disease, no disease progression, less than 50% decrease in donor cell chimerism from last measurement, and the patient is not taking immunosuppressive agents, then donor leukocyte infusions are administered on days 70, 194, and 306. Patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Must have a 6 antigen HLA identical related donor and one of the following diseases: Acute myelogenous leukemia in high risk first complete remission or second or greater complete remission; Acute lymphocytic leukemia in high risk first complete remission or second or greater remission; Chronic myelogenous leukemia in chronic phase; Indolent non-Hodgkin's lymphoma (NHL) or aggressive NHL in complete or partial remission, not eligible for autologous bone marrow transplant (ABMT); Multiple myeloma in complete or partial response; Myelodysplastic syndrome; Stage III or IV chronic lymphocytic leukemia; Hodgkin's disease after first complete remission
• Patients must also have one of the following high risk features: Age 55-70; Age 18-54 must have one of the following conditions: LVEF 35-44%; FEV1 or FVC 40-49%; Bilirubin 2.1-3.0 mg/dL, AST 71-175, or ALT 81-200; Creatinine 2.1-3.0 mg/dL; Disease recurrence less than 1 year after ABMT; Between 18 to 24 months of prior chemotherapy (12 to 24 months for multiple myeloma)

--Prior/Concurrent Therapy--

• See Disease Characteristics

--Patient Characteristics--

• Age: 18 to 70
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin less than 3.1 mg/dL
• Renal: Creatinine less than 3.1 mg/dL
• Cardiovascular: LVEF at least 35%
• Pulmonary: FEV1 and FVC at least 40% of predicted (60% for patients who have received thoracic or mantle radiotherapy)
• Other: Not pregnant; Fertile patients must use effective contraception; Not HIV positive

Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231-2410,  United States

Study chairs or principal investigators

Ephraim J. Fuchs,  Study Chair,  Johns Hopkins Oncology Center   

Study ID Numbers:  CDR0000066639; JHOC-98070603; NCI-H98-0023; JHOC-9845
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003572
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08