RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of T cell removal to prevent graft-versus-host disease in patients who are undergoing bone marrow transplantation from a donor.

Condition	Treatment or Intervention	Phase
Leukemia Multiple Myeloma	Drug: anti-thymocyte globulin  Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Drug: leucovorin calcium  Drug: methotrexate  Drug: methylprednisolone	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the incidence and severity of graft vs host disease (GVHD) following allogeneic bone marrow transplantation with marrow grafts modified by T cell depletion with counterflow centrifugal elutriation and CD34+ cell selection in patients at high risk for GVHD. II. Determine the incidence of graft failure following this treatment regimen in this patient population. III. Determine the relapse rate and overall survival in this patient population treated with this regimen.

PROTOCOL OUTLINE: Patients with unrelated donors, mismatched related donors, or matched related donors diagnosed with acute lymphocytic leukemia, chronic lymphocytic leukemia, myeloma, or advanced acute myeloid leukemia (AML), receive cyclophosphamide IV over 60 minutes on days -6 and -5 and fractionated total body irradiation (TBI) 3 times a day on days -3 through -1, and twice on day 0. Patients receive graft vs host disease (GVHD) prophylaxis with anti-thymocyte globulin (ATG) IV over 8 hours on days -2 and -1. Patients undergo allogeneic bone marrow transplantation (ABMT) on day 0 with marrow grafts modified by T cell depletion with counterflow centrifugal elutriation and CD34+ selection. Patients unable to receive TBI due to matched or mismatched related donors, or age (56 to 60), or patients diagnosed with AML-CR1, chronic myelogenous leukemia, myelodysplastic syndrome, or myeloproliferative disorders with matched related donors, receive oral busulfan every 6 hours on days -7 through -4, cyclophosphamide IV over 60 minutes on days -3 and -2, and ATG IV over 8 hours on days -2 and -1 for GVHD prophylaxis. Patients undergo T cell depleted ABMT on day 0. At pretransplantation, patients with acute leukemia receive intrathecal (IT) methotrexate (MTX) following lumbar puncture. At 48 hours following IT MTX, patients with CNS involvement receive a second dose of IT MTX followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with prior CNS involvement receive cranial radiotherapy for 2 weeks. Following AMBT, patients undergo GVHD prophylaxis consisting of methylprednisolone IV every 12 hours on days 5-22, and then once daily on days 23-28 and cyclosporine IV or orally twice daily beginning on day -1 and continuing until 7-9 months following ABMT. Patients are followed every 3 months until death.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

Ages Eligible for Study:  15 Years   -   60 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed malignancy
• Acute myeloid leukemia (AML) Complete remission 1 (CR1): high risk defined by poor cytogenetics (e.g., deletions, additions, or multiple abnormalities) Complete remission 2 (CR2); Induction failures; Relapse: at least one reinduction attempt if at least 10% marrow blasts
• Acute lymphocytic leukemia CR1: high risk defined by overt CNS involvement or poor cytogenetics (e.g., additions, deletions, translocations, or multiple abnormalities); CR2; Induction failures; Relapse as for AML
• Chronic myelogenous leukemia; Chronic phase (CP) 1; Accelerated phase (AP)/CP2: blast phase patients require induction and achievement of a second chronic phase prior to transplantation
• Chronic lymphocytic leukemia; Relapse: any stage and must have received no greater than 3 regimens since diagnosis
• Multiple myeloma; Primary refractory disease at diagnosis; Relapse (no greater than 2): sensitive disease; Plasma cell leukemia; Inability to achieve a complete remission or relapse after autologous transplantation (no greater than 40 years)
• Myelodysplasia; All FAB subtypes
• Myeloproliferative disorders; Poor response to medical therapy OR Cytogenetic abnormalities
• Severe aplastic anemia (SAA) (for unrelated and/or mismatched donors); Very SAA at diagnosis OR SAA: induction failures
• One antigen mismatch (recipient age 15 to 55); Related donors may be A, B, or DR mismatched; Unrelated donors may be A or B mismatched (DRB1 match)
• Phenotypic (6 out of 6) match; Recipient age 51 to 60 if related donor; Recipient age 41 to 55 if unrelated donor

--Prior/Concurrent Therapy--

• See Disease Characteristics

--Patient Characteristics--

• Age: 15 to 60
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2.0 mg/dL; SGOT/SGPT no greater than 3 times normal; PT/PTT normal
• Renal: Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 60 mL/min
• Cardiovascular: LVEF at least 45% by MUGA scan or echocardiography; Greater than 6 months since myocardial infarction; No uncontrolled arrhythmias
• Pulmonary: FEV1 and DCLO at least 50% predicted
• Other: No psychosocial conditions that would preclude study; No uncontrolled diabetes mellitus; No uncontrolled thyroid disease; No active serious infections; HIV negative; Not pregnant or nursing; Negative pregnancy test

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612,  United States

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000067804; MCC-11587; NCI-G00-1781; MCC-IRB-4599
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00005641
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08