RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: This phase II trial is studying how well donor bone marrow transplantation works in treating patients with hematologic cancers.

Condition	Treatment or Intervention	Phase
acute leukemia atypical chronic myeloid leukemia chronic leukemia chronic myeloproliferative disorders myelodysplastic and myeloproliferative disease plasma cell neoplasm	Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Drug: etoposide  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: graft versus host disease prophylaxis/therapy  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the progression free survival (PFS) and overall survival (OS) of patients with low risk myeloid disorders or older allogeneic recipients who are treated with high dose busulfan and cyclophosphamide and allogeneic bone marrow transplantation (BMT).
• Determine the PFS and OS in patients with lymphoid and high risk myeloid disorders who are treated with etoposide, total body irradiation, and allogeneic BMT.
• Evaluate the toxicities of these 2 regimens when combined with cyclosporine and methotrexate as graft versus host disease prophylaxis in these patients.
• Evaluate the PFS and OS of allogeneic BMT in patients with multiple myeloma and chronic lymphocytic leukemia.

OUTLINE:

• Regimen A: Patients with chronic myelogenous leukemia (CP1, AP/CP2) and other myeloproliferative disorders, myelodysplastic disorders, acute myelogenous leukemia (CR1), or multiple myeloma (not eligible to receive total body irradiation due to prior radiation) are treated with high dose busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation (BMT). Patients receive oral busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Allogeneic bone marrow is infused on day 0.
• Regimen B: Patients with acute myelogenous leukemia (at least CR2, relapsed), acute lymphoid leukemia (ALL), any acute leukemia with CNS involvement, multiple myeloma, or chronic lymphocytic leukemia are treated with total body irradiation and etoposide followed by allogeneic BMT. Patients receive total body irradiation (TBI) on days -7 to -4 for a total of 11 fractions and etoposide IV over 4 hours on day -3. Male patients with ALL receive a testicular boost in 2 fractions on 2 successive days during TBI. Allogeneic bone marrow is infused on day 0. Patients in both regimens receive cyclosporine and methotrexate as graft versus host disease prophylaxis.

Patients are followed weekly for 3 months and then monthly for 1 year.

PROJECTED ACCRUAL: At least 50 patients with low risk myeloid disease, 50 patients with lymphoid malignancies, and 60 patients with high risk myeloid disease will be accrued for this study.

Ages Eligible for Study:  15 Years   -   55 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of:
• Acute myelogenous leukemia
• Complete remission (CR) 1 - ALL except good cytogenetics defined as [(inv16, t(8,21), t(15,17)]
• CR2
• Induction failures
• Relapsed OR
• Acute lymphocytic leukemia (ALL)
• CR1 - high risk defined as overt CNS involvement, 1 or more risk factors (age 30 and over, WBC at least 20,000/mm^3, at least 4 weeks to CR1, myeloid phenotype)
• CR2
• Induction failures
• Relapsed OR
• Chronic myelogenous leukemia
• Chronic phase (CP) 1
• Accelerated phase (AP)/CP2 OR
• Chronic lymphocytic leukemia
• At diagnosis - RAI stage III/IV or Binet C
• Must undergo 1 induction regimen
• Relapsed - any stage
• Must have received no more than 3 regimens for diagnosis OR
• Multiple myeloma
• At diagnosis - stage II/III (primary refractory or sensitive)
• Relapsed no more than 2 times - sensitive disease
• Plasma cell leukemia OR
• Myelodysplasia
• All subtypes eligible OR
• Myeloproliferative disorders
• Poor response to medical therapy OR
• Cytogenetic abnormalities
• Must have a related donor who is genotypic 6 out of 6 HLA A, B, and DR match
• Molecular DR matching required

PATIENT CHARACTERISTICS: Age:

• 15 to 55

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT/SGPT no greater than 3 times upper limit of 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
• No myocardial infarction within the past 6 months
• No arrhythmias controlled by therapy

Pulmonary:

• FEV_1 at least 50% predicted
• DLCO at least 50% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• No diabetes mellitus or thyroid disease that is not medically controlled
• No psychosocial disorder that would preclude study compliance
• No active serious infections
• HIV negative
• Donor must be HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

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:  CDR0000067767; MCC-11281; MCC-IRB-4188; NCI-G00-1759; NCT00005797
Record last reviewed:  July 2004
Last Updated:  February 7, 2005
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005797
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08