Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 to 75 Pharmaceutical / Industry UTSMC-0799296 AMGEN-UTSMC-0799296, IBMTR-SC-00-03.1, ROCHE-UTSMC-0799296, SPRI-UTSMC-0799296, NCI-V02-1705, NCT00044954

Objectives

1. 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).
2. 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.
3. Determine the incidence and extent of graft-versus-host disease, regimen-related toxicity, and engraftment in patients treated with these regimens.
4. Assess the quality of life of patients treated with these regimens.

Entry 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

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

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Robert Collins, MD, Protocol chair		Ph: 214-648-4155; 866-460-4673 Email: robert.collins@utsouthwestern.edu

Registry Information
Official Title		Low Dose Total-Body Irradiation And Fludarabine Followed By HLA Matched Allogeneic Stem Cell Transplantation For Hematologic Malgnancies - A Multi-Center Study
Trial Start Date		2001-11-12
Registered in ClinicalTrials.gov		NCT00044954
Date Submitted to PDQ		2002-05-29
Information Last Verified		2005-02-04

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