RATIONALE: Bone marrow from donors may be able to treat patients with severe aplastic anemia and patients whose bodies have rejected previous bone marrow transplantation.

PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have severe aplastic anemia or whose bodies have rejected previous bone marrow transplant.

Condition	Treatment or Intervention	Phase
Lymphoma Multiple Myeloma Leukemia	Drug: anti-thymocyte globulin  Drug: cyclophosphamide  Drug: cyclosporine  Drug: filgrastim  Drug: methylprednisolone  Drug: monoclonal antibody OKT3	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the graft failure rate and overall survival of patients with severe aplastic anemia after receiving an allogeneic bone marrow transplant.

II. Determine the efficacy of high dose cyclophosphamide and anti-thymocyte globulin as conditioning regimen for a second bone marrow transplant in patients who reject their first graft.

III. Determine the efficacy of methylprednisolone and anti-CD3 monoclonal antibody as a conditioning regimen for a second bone marrow transplant in patients who reject their first graft and are poor candidates for cyclophosphamide and anti-thymocyte globulin.

PROTOCOL OUTLINE: Patients with graft failure with the following organ function and performance status are assigned to arm I: Performance status: Karnofsky 60-100% Pulmonary: FEV1 and DLCO at least 50% Cardiac: Left ventricular ejection fraction at least 45% Hepatic: None to mild venoocclusive disease

Patients with graft failure with the following organ function and performance status are assigned to arm II: Performance status: Karnofsky 20-50% Pulmonary: FEV1 or DLCO less than 50% Cardiac: Left ventricular ejection fraction less than 45% Hepatic: Moderate to severe venoocclusive disease

Patients with aplastic anemia are assigned to arm I.

Arm I: Patients receive cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV over 8 hours on days -5 to -3, and bone marrow transplant on day 0.

Arm II: Patients receive methylprednisolone IV twice a day on days -5 to 62; monoclonal antibody OKT3 IV on days -1 to 24; bone marrow transplant on day 0; oral cyclosporine twice a day starting day 20; and filgrastim (G-CSF) subcutaneously once a day starting day -5 until blood counts recover.

Patients are followed once a week for 3 months, and then monthly for one year.

PROJECTED ACCRUAL: A total of 40 patients (20 with aplastic anemia and 20 with graft failure) will be accrued for this study.

Ages Eligible for Study:  15 Years   -   55 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed aplastic anemia; Must have related donor with a genotypic 6 out of 6 HLA A, B, and DR match OR Bone marrow transplant failure; Must have related donor with at least a 5 out of 6 HLA match OR Must have an unrelated donor with at least a 5 out of 6 HLA match

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics
• Chemotherapy: Not specified
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 15 to 55
• Performance status: Aplastic anemia patients: Karnofsky 80-100%; Graft failure patients: Karnofsky 20-100%
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Aplastic anemia patients: Bilirubin no greater than 2.0 mg/dL; SGOT/SGPT no greater than 3 times normal; PT/PTT normal (except when aplastic anemia secondary to viral hepatitis); Graft failure patients: Mild to severe venoocclusive disease allowed
• Renal: Aplastic anemia patients: Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 60 mL/min
• Cardiovascular: Aplastic anemia patients: Left ventricular ejection fraction at least 45% by MUGA or echocardiography; No myocardial infarction within the past 6 months; No uncontrolled arrhythmias
• Pulmonary: Aplastic anemia patients: FEV1 and DLCO at least 50% predicted
• Other: Aplastic anemia patients: No uncontrolled diabetes mellitus or thyroid disease; No active serious infections; HIV negative; Not pregnant or nursing; Negative pregnancy test; No psychosocial problem that would preclude study compliance

Study chairs or principal investigators

Steven C. Goldstein,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000067876; MCC-11309; NCI-G00-1791; MCC-IRB-4251
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005852
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08