RATIONALE: Peripheral stem cell transplantation replaces immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment of the cells with a monoclonal antibody may prevent this from happening.

PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation plus monoclonal antibody therapy in treating patients who have high-risk hematologic cancer, refractory breast or kidney cancer, or melanoma.

Condition	Treatment or Intervention	Phase
Breast Cancer hematopoietic and lymphoid cancer kidney and urinary cancer skin tumor	Drug: alemtuzumab  Drug: cyclophosphamide  Drug: filgrastim  Drug: fludarabine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: in vitro-treated peripheral blood stem cell transplantation  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation	Phase II

OBJECTIVES:

• Determine the efficacy, in terms of mortality, occurrence of acute graft versus-host-disease, and grade 3/4 toxicity, of in vivo and in vitro alemtuzumab (monoclonal antibody CD52; Campath-1H) administered concurrently with nonmyeloablative fludarabine and cyclophosphamide, followed by HLA identical matched sibling allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies or refractory breast or renal cell cancer or melanoma.
• Determine the engraftment rate, response rate, and long term survival of patients receiving this regimen.
• Determine the recovery of immune function post engraftment in patients treated with this regimen.
• Determine the pharmacokinetics of cyclophosphamide administered in this regimen.
• Assess graft-versus-tumor effects in patients treated with this regimen.

OUTLINE: Patients receive alemtuzumab (monoclonal antibody CD52; Campath-1H) IV over 3 hours on days -6 to -2 and fludarabine IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -2. Allogeneic peripheral blood stem cells and alemtuzumab are infused on days 0 and 1. Filgrastim (G-CSF) is administered subcutaneously beginning on day 1 and continuing until blood counts recover.

Patients are followed daily until day 60, twice a week until day 100, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of any one of the following:
• Relapsed or refractory hematologic malignancy
• Acute myeloid leukemia
• Chronic myeloid leukemia
• Acute lymphocytic leukemia
• Chronic lymphocytic leukemia
• Multiple myeloma
• Myeloproliferative or myelodysplastic disorders
• Not eligible for full myeloablative matched sibling transplant
• Bone marrow failure
• Severe or very severe aplastic anemia
• Myelofibrosis or paroxysmal nocturnal hemoglobinuria
• Increased blast cells (at least 5%) in peripheral blood or bone marrow OR
• Visceral organ damage due to disease
• Severe fibrosis of bone marrow
• Severe Budd-Chiari
• Mild hepatic/portal clot by ultrasound or hepatic biopsy
• Drug induced marrow aplasia
• Hemoglobinopathies
• Severe sickle cell anemia
• Thalassemia with cardiac or hepatic damage
• Solid tumor with metastatic disease and failed at least 1 standard regimen
• Breast cancer
• Progressed after doxorubicin and cyclophosphamide
• Renal cell cancer
• Failed interleukin-2 therapy
• Melanoma
• Failed interleukin-2 therapy
• Must have 6/6 HLA matched sibling donor
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• 18 and over

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• CALGB 0-2

Life expectancy:

• At least 6 weeks

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• Ejection fraction greater than 40%

Pulmonary:

• DLCO greater than 40%

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other major medical or psychiatric illness that would preclude compliance
• No allergy to murine protein
• HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• Recovered from prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Recovered from prior radiotherapy

Surgery:

• Not specified

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting

Study chairs or principal investigators

David A. Rizzieri, MD,  Study Chair,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067374; DUMC-1340-99-7; NCI-G99-1617
Record last reviewed:  April 2002
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004143
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-18