RATIONALE: Monoclonal antibodies such as alemtuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Donor peripheral stem cell transplantation may be able to replace immune cells that were destroyed by anticancer therapy. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Giving mycophenolate mofetil, cyclosporine, fludarabine, and donor white blood cells may prevent this from happening.

PURPOSE: Phase I trial to study the effectiveness of combining alemtuzumab, total-body irradiation, and fludarabine followed by donor peripheral stem cell transplantation in treating patients who have hematologic cancer.

Condition	Treatment or Intervention	Phase
childhood Hodgkin's lymphoma childhood non-Hodgkin's lymphoma hematopoietic and lymphoid cancer	Drug: alemtuzumab  Drug: allogeneic lymphocytes  Drug: cyclosporine  Drug: fludarabine  Drug: mycophenolate mofetil  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: graft versus tumor induction  Procedure: leukocyte therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase I

OBJECTIVES:

• Determine the optimum dose of alemtuzumab administered with low-dose total body irradiation and fludarabine followed by HLA class I mismatched allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.
• Determine whether stable allogeneic engraftment can be safely achieved in patients treated with this regimen.
• Determine the risk of occurrence of acute and chronic graft-vs-host disease in patients treated with this regimen.
• Determine the risk and incidence of infections in patients treated with this regimen.
• Determine whether engraftment can be maintained in patients treated with fludarabine, donor lymphocyte infusion, mycophenolate mofetil, and cyclosporine.
• Determine the risk of disease progression and relapse in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of alemtuzumab.

Patients receive alemtuzumab IV on days -8 to -5 and fludarabine IV on days -4 to -2. Patients undergo low-dose total body irradiation followed by allogeneic peripheral blood stem cell transplantation on day 0. Patients receive graft-vs-host disease (GVHD) prophylaxis comprising oral cyclosporine twice daily on days -3 to 180 followed by a taper until day 365 and oral mycophenolate mofetil three times daily on days 0 to 100 followed by a taper until day 156. After day 28, patients with low donor chimerism and no GVHD may receive additional fludarabine IV once followed 2 days later by one donor lymphocyte infusion.

Cohorts of 7-14 patients receive escalating doses of alemtuzumab until the optimum dose is determined. The optimum dose is defined as the dose at which no more than 1 of each 7 patients experiences graft rejection or unacceptable toxicity.

Patients are followed at 4 months, 6 months, every 6 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  up to  74 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of hematologic malignancy that is ineligible for (or patient refused) conventional transplantation and expected to be stable for at least 100 days without chemotherapy
• Diffuse large B-cell non-Hodgkin's lymphoma (NHL), meeting 1 of the following criteria:
• Ineligible for autologous stem cell transplantation (SCT)
• Failed prior autologous SCT
• Low-grade NHL
• Less than 6 months duration of complete response between courses of prior conventional therapy
• Chronic lymphocytic leukemia
• Failed 2 lines of prior conventional therapy
• Refractory to fludarabine
• Hodgkin's lymphoma
• Failed prior frontline therapy
• Failed or ineligible for prior autologous transplantation
• Multiple myeloma, meeting 1 of the following criteria:
• Received prior chemotherapy
• Failed prior autografting
• No autografting immediately prior to nonmyeloablative SCT
• Acute myeloid leukemia
• Less than 5% marrow blasts
• Acute lymphoblastic leukemia
• Less than 5% blasts
• Chronic myelogenous leukemia
• Greater than first chronic phase OR accelerated phase if failed prior therapy with imatinib mesylate or SCT
• Myelodysplastic syndromes
• Failed prior chemotherapy
• Less than 10% marrow blasts
• Myeloproliferative disorders
• Related or unrelated donor
• Best available match is an HLA class II DRB1 and DQB1 matched donor who is incompatible for 1 of the following:
• Any single serologically detectable class I HLA-A, -B, or -C mismatch
• One additional allele level class I mismatch allowed
• Any combination of 2 allele level mismatches
• Likelihood of rapid disease progression during HLA typing exists and a completely matched unrelated donor is not found
• No HLA-A, -B, or -C single locus allelic mismatched related donor available
• No indication for autologous transplantation as a treatment option
• No CNS involvement with disease refractory to intrathecal chemotherapy NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age:

• Under 75

Performance status:

• Karnofsky 70-100% (adults) OR
• Lansky 50-100% (children)

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No fulminant liver failure
• No liver cirrhosis with evidence of portal hypertension
• No alcoholic hepatitis
• No chronic viral hepatitis (bilirubin greater than 3 mg/dL)
• No hepatic encephalopathy
• No biliary obstruction
• No symptomatic biliary disease
• No bacterial or fungal liver abscess
• No uncorrectable hepatic synthetic dysfunction (prolonged PT)
• No ascites related to portal hypertension

Renal:

• Not specified

Cardiovascular:

• No symptomatic coronary artery disease
• No poorly controlled hypertension on multiple antihypertensives
• No other cardiac failure requiring therapy
• Ejection fraction at least 35% (required if patient received prior anthracyclines or had prior cardiac disease)

Pulmonary:

• No supplementary continuous oxygen
• DLCO at least 35%

Other:

• HIV negative
• No severe limitation of life expectancy due to diseases other than malignancy
• No fungal infections with radiological progression after amphotericin B or active triazole for more than 1 month
• No esophageal varices
• No history of bleeding esophageal varices
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for up to 1 year after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• No concurrent post-transplantation growth factors during the first 28 days of mycophenolate mofetil administration

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80010,  United States; Recruiting
Texas
      Texas Oncology PA (TOPA) at Baylor-Sammons, Dallas,  Texas,  75246,  United States; Recruiting
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
Germany
      Universitaet Leipzig, Leipzig,  D-04103,  Germany; Recruiting
Italy
      University of Turin, Turin,  10126,  Italy; Recruiting

Study chairs or principal investigators

Brenda Sandmaier, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000069412; FHCRC-1591.00; NCI-H02-0089
Record last reviewed:  March 2004
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00040846
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-29