RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or total-body irradiation used to kill leukemia and lymphoma cells. Bone marrow transplantation using donated bone marrow may be an effective treatment for malignant or nonmalignant hematologic disorders.

PURPOSE: This phase II trial is studying how well donor bone marrow transplantation works in treating patients with leukemia, lymphoma, or nonmalignant hematologic disorders.

Condition	Treatment or Intervention	Phase
acute leukemia atypical chronic myeloid leukemia chronic leukemia chronic myeloproliferative disorders myelodysplastic and myeloproliferative disease plasma cell neoplasm	Drug: cyclophosphamide  Drug: leucovorin calcium  Drug: methotrexate  Procedure: allogeneic bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the survival of allogeneic bone marrow transplantation using closely matched related and unrelated donors in patients with malignant or nonmalignant hematological disorders.
• Determine the incidence and severity of acute and chronic graft versus host disease with this treatment regimen in these patients.
• Determine the relapse rates with this treatment regimen in those patients with malignant disorders.
• Determine the incidence and severity of infectious complications associated with this treatment regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days -6 and -5, total body radiotherapy on days -3 through 0, and allogeneic bone marrow transplantation on day 0.

Patients with acute lymphocytic leukemia (ALL) receive intrathecal methotrexate at the beginning of the study. If CNS involvement is documented, patients receive a second dose of methotrexate 48 hours later followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with ALL and/or CNS involvement receive intrathecal methotrexate every other week for 12 weeks after transplant.

Patients with prior CNS involvement receive radiotherapy for 2.5 weeks prior to transplant. Patients with ALL receive total body radiotherapy for 5 consecutive days prior to transplant.

Patients are followed once a week for 3 months, and then monthly for 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 6 years.

Ages Eligible for Study:  15 Years   -   50 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of one of the following:
• Acute lymphocytic leukemia (ALL):
• Complete remission (CR) 1 - high risk defined as overt CNS involvement or poor cytogenetics (additions, deletions, translocations, or multiple abnormalities)
• CR2
• Induction failures
• Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt
• Acute myelogenous leukemia (AML):
• CR1 - high risk defined as poor cytogenetics (deletions, additions, multiple abnormalities)
• CR2
• Induction failures
• Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt
• Chronic myelogenous leukemia (CML):
• Chronic phase (CP) 1
• Accelerated phase/CP2 - patients in blast phase must undergo treatment and achieve a second chronic phase prior to transplant
• Chronic lymphocytic leukemia (CLL):
• Relapse - any stage; must have received no more than 3 prior regimens
• Multiple myeloma:
• At diagnosis - primary refractory
• Relapse (no more than 2) - sensitive disease
• Plasma cell leukemia
• Inability to achieve a complete remission after autologous transplant (no older than 40)
• Myelodysplasia - all subtypes
• Myeloproliferative disorders - patients with poor response to medical therapy or cytogenetic abnormalities
• Severe aplastic anemia (SAA):
• Very SAA - at diagnosis
• SAA - induction therapy
• Donors must be a phenotypic (6 out of 6) match or a one antigen (A or B) mismatch

PATIENT CHARACTERISTICS: Age:

• 15 to 50

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT and 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:

• Left ventricular ejection fraction at least 45%
• No myocardial infarction within past 6 months
• No uncontrolled arrhythmias

Pulmonary:

• FEV1 at least 50%
• DLCO at least 50% predicted

Other:

• No active serious infection
• HIV negative
• Not pregnant or nursing
• No uncontrolled diabetes mellitus or thyroid disease

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States; Recruiting

Study chairs or principal investigators

Teresa Field, MD, PhD,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000067763; MCC-11282; MCC-IRB-4189; NCI-G00-1755; NCT00005622
Record last reviewed:  July 2004
Last Updated:  February 7, 2005
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00005622
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08