RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Tacrolimus and mycophenolate mofetil may prevent this from happening.

PURPOSE: This phase II trial is studying how well giving chemotherapy, tacrolimus, mycophenolate mofetil, and radiation therapy together with allogeneic bone marrow transplantation works in treating patients with hematologic cancer.

Condition	Treatment or Intervention	Phase
childhood Hodgkin's lymphoma childhood non-Hodgkin's lymphoma Leukemia Lymphoma myelodysplastic and myeloproliferative diseases plasma cell neoplasm	Drug: cyclophosphamide  Drug: filgrastim  Drug: fludarabine  Drug: mycophenolate mofetil  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: graft versus tumor induction  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of combined immunosuppression before and after nonmyeloablative HLA-haploidentical bone marrow transplantation, in terms of donor engraftment at day 84, in patients with high-risk hematologic malignancies.
• Determine the safety of this regimen, in terms of incidence and severity of graft-vs-host disease and non-relapse-related mortality at day 200, in these patients.

OUTLINE:

• Conditioning regimen: Patients receive fludarabine IV over 1 hour on days -6 to -2, cyclophosphamide IV over 1 hour on days -6 and -5, and total body irradiation on day -1.
• Bone marrow infusion: Bone marrow from an HLA-haploidentical donor is infused on day 0.
• Post-transplant immunosuppression: Patients receive cyclophosphamide IV over 1 hour on day 3.
• Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV over 4 hours or orally (when tolerated) beginning on day 4 and continuing until day 180 in the absence of GVHD. Oral mycophenolate mofetil is administered three times daily on days 4-35. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 4 and continuing until blood counts recover.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 15-30 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of any of the following hematologic malignancies:
• Chronic myelogenous leukemia in accelerated phase
• Acute myeloid leukemia (AML) in first complete remission (CR) with the following high-risk cytogenetics:
• del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22), complex karyotypes (at least 3 abnormalities)
• AML in at least second CR with less than 5% marrow blasts
• High-risk acute lymphoblastic leukemia with less than 5% marrow blasts
• First CR with the following high-risk cytogenetics:
• t(9;22), t(4;11), or hypodiploid (less than 45 chromosomes) for children
• t(9;22), t(8;14), t(4;11), t(1;19) for adults
• More than 4 weeks to achieve first CR
• At least second CR
• Myelodysplastic syndromes after at least 1 prior course of induction chemotherapy and less than 5% marrow blasts
• Stage II or III multiple myeloma
• Progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT)
• No autograft immediately before nonmyeloablative HSCT (tandem approach)
• Chronic lymphocytic leukemia, non-Hodgkin's lymphoma, or Hodgkin's lymphoma
• Ineligible for or failed autologous HSCT
• Disease must be expected to be stable for at least 100 days without chemotherapy
• Related donor available
• Identical for 1 HLA haplotype and mismatched at the HLA-A, -B, -C, or DRB1 loci of the unshared haplotype
• No single HLA-A, -B, or -C allele mismatches
• No HLA-mismatch only in the HVG direction
• Not cross-match positive
• No suitably matched related or unrelated donor
• No conventional transplantation options
• No CNS involvement refractory to intrathecal chemotherapy

PATIENT CHARACTERISTICS: Age

• Any age

Performance status

• Karnofsky 60-100% (adults)
• Lansky 60-100% (children)

Life expectancy

• Not severely limited by disease other than malignancy

Hematopoietic

• See Disease Characteristics

Hepatic

• No fulminant liver failure
• No cirrhosis of the liver with portal hypertension
• No alcoholic hepatitis
• No esophageal varices
• No hepatic encephalopathy
• No uncorrectable hepatic synthetic dysfunction (prolonged prothrombin time)
• No ascites related to portal hypertension
• No bacterial or fungal liver abscess
• No biliary obstruction
• No chronic viral hepatitis
• No symptomatic biliary disease
• Bilirubin no greater than 3 mg/dL

Renal

• Not specified

Cardiovascular

• LVEF at least 35%

Pulmonary

• DLCO at least 35%
• No concurrent supplemental continuous oxygen

Other

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after study participation
• No active serious infection (e.g., mucormycosis, uncontrolled aspergillosis, or tuberculosis)

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics
• No prior allogeneic HSCT unless allograft was rejected and there is no evidence of donor hematopoietic engraftment

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

Paul V. O'Donnell, MD, PhD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000258112; FHCRC-1667.00; NCI-H02-0098; NCT00049504
Record last reviewed:  February 2005
Last Updated:  February 15, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049504
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08