Treatment of Bone Marrow to Prevent Graft-Versus-Host Disease in Patients With Acute or Chronic Leukemia Undergoing Bone Marrow Transplantation

July 9, 2013 updated by: Chimeric Therapies

A Multi-Center, Open Label, Randomized, Active Controlled Phase II/III Clinical Trial to Evaluate the Safety and Efficacy of Processed Unrelated Bone Marrow in Patients With Acute or Chronic Leukemia

RATIONALE: Bone marrow that has been treated to remove certain white blood cells may reduce the chance of developing graft-versus-host disease following bone marrow transplantation.

PURPOSE: Randomized phase II/III trial to compare the effectiveness of treated bone marrow with that of untreated bone marrow in preventing graft-versus-host disease in patients with acute or chronic leukemia who are undergoing bone marrow transplantation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the efficacy of processed (cell depleted) vs unprocessed (conventional) unrelated bone marrow transplantation in reducing grade III/IV acute graft vs host disease (GVHD) in patients with acute or chronic leukemia or myelodysplastic syndromes.
  • Compare the safety of these regimens in these patients.
  • Compare the disease-free survival rate at 100 days and at 6 months in patients treated with these regimens.
  • Compare the time to engraftment and percent engraftment in patients treated with these regimens.
  • Compare the reduction rate of grade II or greater acute and chronic GVHD in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to degree of HLA matching and disease (chronic vs acute). Acute myelogenous leukemia patients are further stratified according to prior myelodysplastic syndromes (yes vs no). Patients are randomized to one of two bone marrow transplantation arms.

All patients receive a conditioning regimen comprising fludarabine IV on day -6, cyclophosphamide IV on days -5 and -4, anti-thymocyte globulin IV on days -4 and -2, and total body irradiation on days -3 to 0. Patients also receive methylprednisolone IV every 12 hours for 4 doses on days -2 to 0. Tacrolimus IV is administered continuously on day -1 and continues either orally or IV for 6 months. Bone marrow is infused on day 0. Filgrastim (G-CSF) is administered subcutaneously from day 0 until blood counts recover.

  • Arm I: Patients receive allogeneic bone marrow that has been processed to produce a mononuclear cell preparation.
  • Arm II: Patients receive unprocessed allogeneic bone marrow. Patients are followed weekly for 100 days and then at 6 months.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 17 months.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 3

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
    • California
      • La Jolla, California, United States, 92093-0658
        • University of California San Diego Cancer Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Presbyterian-St Luke's Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Cancer Center
    • Florida
      • Gainesville, Florida, United States, 32610-100277
        • Shands Hospital and Clinics, University of Florida
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Blood and Marrow Transplantation
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • James Graham Brown Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Cancer Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73190
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97201-3098
        • Oregon Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102-1192
        • Hahnemann University Hospital
    • Texas
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • South Texas Cancer Institute
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Massey 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

12 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following:

    • Acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in first early relapse, second remission, or subsequent remission

    • AML in first complete remission with one of the following adverse features:

      • Antecedent hematologic disorder such as myelodysplasia
      • AML resulting from prior chemotherapy or radiotherapy
      • More than 1 course of induction chemotherapy to achieve remission or adverse cytogenetics such as Philadelphia chromosome 9:22, +8, +11; abnormal 12p; or deletions of chromosomes 5, 7, or 20 (3:3)

    • ALL in first complete remission with poor risk cytogenetics such as

      • Philadelphia chromosome 9:22, 8:14, or 4:11 OR
      • WBC greater than 100,000/mm3 OR
      • Time to achieve complete remission more than 4 weeks
    • Chronic myelogenous leukemia in chronic or accelerated phase

    • Myelodysplastic syndromes

      • Refractory anemia with excess blasts (RAEB) OR
      • RAEB in transformation

  • Unrelated bone marrow donor available

    • If matched at 6 of 6 HLA-A, -B, and -DR loci, patient must be 12 to 50 years
    • If matched at 5 of 6 loci, patient must be 12 to 35 years
  • No matched sibling donor available
  • No uncontrolled CNS leukemia

PATIENT CHARACTERISTICS:

Age:

  • See Disease Characteristics
  • 12 to 50

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • At least 12 weeks

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin less than 2.5 times upper limit of normal (ULN)
  • SGOT or SGPT less than 2.5 times ULN

Renal:

  • Creatinine no greater than 1.5 mg/dL

Cardiovascular:

  • LVEF greater than 50% without medication

Pulmonary:

  • DLCO and FVC at least 50% predicted

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other serious medical illness
  • No uncontrolled diabetes mellitus
  • No uncontrolled and/or active infection
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 3 weeks since prior immunotherapy and recovered
  • At least 1 year since prior autologous transplantation
  • No prior allogeneic transplantation

Chemotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy (except hydroxyurea) and recovered

Endocrine therapy:

  • At least 3 weeks since prior hormonal therapy and recovered

Radiotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior radiotherapy and recovered
  • No prior radiotherapy at doses that would preclude study

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
  • Allocation: Randomized
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

Chimeric Therapies

Investigators

  • Study Chair: James N. Lowder, MD, Chimeric Therapies

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

March 1, 2000

Study Completion (Actual)

May 1, 2003

Study Registration Dates

First Submitted

January 28, 2000

First Submitted That Met QC Criteria

May 8, 2003

First Posted (Estimate)

May 9, 2003

Study Record Updates

Last Update Posted (Estimate)

July 10, 2013

Last Update Submitted That Met QC Criteria

July 9, 2013

Last Verified

February 1, 2002

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHIMERIC-HM01
  • CDR0000067502 (Registry Identifier: PDQ (Physician Data Query))
  • WSU-10-02-99-M01-FB

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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