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

September 13, 2019 updated by: University of Texas Southwestern Medical Center

Low Dose Total-Body Irradiation And Fludarabine Followed By HLA Matched Allogeneic Stem Cell Transplantation For Hematologic Malgnancies - A Multi-Center Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 1999

Primary Completion (Actual)

November 1, 2006

Study Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

September 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

September 17, 2019

Last Update Submitted That Met QC Criteria

September 13, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000069461
  • UTSMC-0799296
  • AMGEN-UTSMC-0799296
  • IBMTR-SC-00-03.1
  • ROCHE-UTSMC-0799296
  • SPRI-UTSMC-0799296
  • NCI-V02-1705

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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