RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells.

PURPOSE: This phase II trial is studying how well giving bone marrow transplantation from an unrelated donor together with cyclophosphamide and total-body irradiation works in treating patients with hematologic cancer.

Condition	Treatment or Intervention	Phase
Acute Lymphocytic Leukemia Acute Myeloid Leukemia atypical chronic myeloid leukemia Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia myelodysplastic and myeloproliferative disease	Drug: anti-thymocyte globulin  Drug: cyclophosphamide  Drug: filgrastim  Drug: immune globulin  Drug: methotrexate  Drug: sargramostim  Drug: tacrolimus  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: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: high-dose chemotherapy  Procedure: non-specific immune-modulator therapy  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Study the curative potential of high-dose cyclophosphamide and total-body irradiation followed by rescue with bone marrow from volunteer HLA-matched donors in patients with a variety of hematologic malignancies and bone marrow failure states.
• Study the toxic effects associated with matched unrelated bone marrow transplantation in this patient population.
• Participate in collaborative research studies with the National Marrow Donor Program.

OUTLINE: All patients receive myeloablative therapy with high-dose cyclophosphamide and total body irradiation over 4 days; patients with severe aplastic anemia also receive antithymocyte globulin. Patients then undergo allogeneic bone marrow transplantation. Filgrastim (G-CSF) is given after transplant to accelerate engraftment. Sargramostim (GM-CSF) may be given in case of graft failure.

All patients receive graft-versus-host-disease (GVHD) prophylaxis with tacrolimus, methotrexate, and gamma globulin. Established GVHD is treated with corticosteroids and, as necessary, antithymocyte globulin.

Patients are followed at 100 days, 6 months, and 1 year after transplant, then annually thereafter.

PROJECTED ACCRUAL: A total of 10 patients per year will be accrued for this study over 5 years.

Ages Eligible for Study:  17 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• One of the following hematologic malignancies/disorders:
• Acute lymphoblastic leukemia
• In second or subsequent complete remission (CR)
• In first CR with high-risk features (e.g., Philadelphia chromosome-positive)
• In first relapse and failed conventional salvage therapy
• Acute myelogenous leukemia (AML)
• In second or subsequent CR
• In early first relapse
• In full first relapse and failed conventional salvage therapy
• In first CR with high-risk features, e.g., trisomy 8 or FAB 6/7
• Standard-risk AML offered conventional-dose consolidation chemotherapy or autologous bone marrow transplantation
• Chronic myelogenous leukemia in chronic, accelerated, or second chronic phase
• No blast crisis
• Severe aplastic anemia that has failed at least 1 course of immunosuppressive therapy
• Paroxysmal nocturnal hemoglobinuria with high-risk features (e.g., disseminated intravascular coagulation, thrombotic events)
• Myelodysplastic syndrome, i.e.:
• Symptomatic, transfusion-dependent refractory anemia with excess blasts
• (RAEB) or RAEB in transformation
• Secondary leukemia in CR following conventional-dose induction chemotherapy
• Unrelated marrow donor available who is 8 out of 10-, 9 out of 10-, or 10 out of 10-antigen serologically HLA-matched at A, B, C, DRb, and DQB loci by molecular typing
• No CNS malignancy

PATIENT CHARACTERISTICS: Age:

• 17 to 60

Performance status:

• Karnofsky 70-100%

Life expectancy:

• No reduction due to other serious illness

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 3 mg/dL
• AST/ALT no greater than twice normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Left ventricular ejection fraction at least 45%
• No severe hypertension

Pulmonary:

• DLCO, FEV_1, and FVC at least 50%

Other:

• HIV negative
• No active infection at time of transplant
• No advanced diabetes
• No significant neurologic deficit
• No active drug or substance abuse
• No emotional disorders
• Able to participate in frequent medical care for at least 1-2 years
• Willing to comply with National Marrow Donor Program policies

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Pennsylvania
      Fox Chase - Temple Cancer Center, Philadelphia,  Pennsylvania,  19111-2442,  United States; Recruiting

Study chairs or principal investigators

Kenneth F. Mangan, MD,  Study Chair,  Fox Chase Cancer Center   

Study ID Numbers:  CDR0000064937; TUHSC-2803; NCI-V96-0950; NCT00002809
Record last reviewed:  April 2004
Last Updated:  February 24, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002809
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08