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

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

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma myelodysplastic and myeloproliferative diseases plasma cell neoplasm	Drug: allogeneic lymphocytes  Drug: cyclosporine  Drug: fludarabine  Drug: mycophenolate mofetil  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: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response rate and duration of response in patients with low-risk hematologic malignancies treated with low-dose total-body irradiation (TBI) and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a slow immunosuppression taper and donor leukocyte infusions (DLI).
• Determine the response rate and duration of response in patients with high-risk hematologic malignancies treated with low-dose TBI and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a faster immunosuppression taper and DLI.
• Determine the incidence and extent of graft-versus-host disease, regimen-related toxicity, and engraftment in patients treated with these regimens.
• Assess the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups (high-risk vs low-risk hematologic malignancy). The high-risk group includes acute myelogenous leukemia, myelodysplastic syndromes, accelerated phase chronic myelogenous leukemia (CML), second chronic phase CML, and non-Hodgkin's lymphoma. The low-risk group includes Hodgkin's lymphoma, first chronic phase CML, multiple myeloma, and chronic lymphocytic leukemia.

Patients receive fludarabine IV on days -4 to -2. Patients undergo total-body irradiation on day 0 followed by allogeneic stem cell transplantation. Patients also receive oral mycophenolate mofetil on days 0-28.

High-risk patients receive oral cyclosporine twice daily on days -2 to day 60. Patients with persistent disease, T-cell chimerism, and no graft-vs-host disease (GVHD) on day 90 receive up to 3 doses of donor leukocyte infusion (DLI) over the next 4 months.

Low-risk patients receive oral cyclosporine twice daily on days -2 to day 150. Patients with persistent disease, T-cell chimerism, and no GVHD on day 180 receive up to 3 doses of DLI over the next 4 months.

Quality of life is assessed at baseline and at 1, 3, 6, 9, 12, 18, and 24 months.

Patients are followed at 1, 3, 6, 9, and 12 months and then annually for 2 years.

PROJECTED ACCRUAL: A total of 120 patients (60 per group) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following hematologic malignancies:
• Chronic myelogenous leukemia (CML)
• First or second chronic phase
• Accelerated phase
• Acute myelogenous leukemia (AML)
• At least second remission
• First remission allowed if poor-risk features are present (complex chromosome karyotype, abnormalities of chromosomes, especially 5 or 7, 12p-, +13, +8, t[9:11])
• Myelodysplastic syndromes (MDS)
• Intermediate- or high-risk disease by the prognostic scoring system
• Multiple myeloma (MM)
• Hodgkin's lymphoma
• Second or greater relapse
• First relapse allowed if disease-free interval is less than 1 year
• Ineligible for autologous transplantation
• Non-Hodgkin's lymphoma (NHL)
• Grade III follicular large cell (relapsed after one course of prior chemotherapy)
• Diffuse large cell (relapsed after one course of prior chemotherapy)
• Mantle cell
• Chronic lymphocytic leukemia (CLL)
• Relapsed after at least 1 course of prior therapy
• Must have 6 out of 6 HLA A-, B-, and DR- identical sibling donor

PATIENT CHARACTERISTICS: Age

• 18 to 75 for patients with MM
• 50 to 75 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL
• 18 to 49 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL who are considered eligible for an allogeneic bone marrow transplantation (BMT) but do not meet institutional criteria for a standard allogeneic BMT

Performance status

• Zubrod 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 3 mg/dL

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• LVEF at least 40% by MUGA or echocardiogram

Pulmonary

• DLCO at least 50% of predicted

Other

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No recent history of drug or alcohol abuse
• No other prior malignancy except basal cell skin cancer
• No uncontrolled bacterial, viral, fungal, or parasitic infections

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior autologous transplantation allowed if disease progression occurred
• No prior or concurrent tandem autologous transplantation followed by non-myeloablative-allograft protocol

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Colorado
      Rocky Mountain Cancer Centers - Denver Midtown, Denver,  Colorado,  80218,  United States
Florida
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
Georgia
      Blood and Marrow Transplant Group of Georgia, Atlanta,  Georgia,  30342-4777,  United States
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Missouri
      Kansas City Cancer Centers - Central, Kansas City,  Missouri,  64111,  United States
New Jersey
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States
New York
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37212,  United States
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75235-8590,  United States
      Texas Transplant Institute, San Antonio,  Texas,  78229,  United States
Virginia
      Massey Cancer Center at Virginia Commonwealth University, Richmond,  Virginia,  23298-0037,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Study chairs or principal investigators

Robert H. Collins, MD,  Study Chair,  Simmons Cancer Center   

Study ID Numbers:  CDR0000069461; UTSMC-0799296; AMGEN-UTSMC-0799296; IBMTR-SC-00-03.1; ROCHE-UTSMC-0799296; SPRI-UTSMC-0799296; NCI-V02-1705; NCT00044954
Record last reviewed:  January 2005
Last Updated:  January 12, 2005
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00044954
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08