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

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ClinicalTrials.gov Identifier: NCT00004255
Recruitment Status : Completed
First Posted : May 9, 2003
Last Update Posted : July 10, 2013
Sponsor:
Information provided by:
National Cancer Institute (NCI)

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Biological: anti-thymocyte globulin Biological: filgrastim Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methylprednisolone Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: in vitro-treated bone marrow transplantation Radiation: radiation therapy Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2000
Actual Study Completion Date : May 2003

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Arms and Interventions
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Outcome Measures
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Eligibility Criteria
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Ages Eligible for Study:   12 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004255


Locations
United States, California
University of California San Diego Cancer Center
La Jolla, California, United States, 92093-0658
United States, Colorado
Presbyterian-St Luke's Medical Center
Denver, Colorado, United States, 80218
United States, District of Columbia
Lombardi Cancer Center
Washington, District of Columbia, United States, 20007
United States, Florida
Shands Hospital and Clinics, University of Florida
Gainesville, Florida, United States, 32610-100277
United States, Indiana
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, United States, 46202
United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, New York
University of Rochester Cancer Center
Rochester, New York, United States, 14642
New York Medical College
Valhalla, New York, United States, 10595
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73190
United States, Oregon
Oregon Cancer Center
Portland, Oregon, United States, 97201-3098
United States, Pennsylvania
Hahnemann University Hospital
Philadelphia, Pennsylvania, United States, 19102-1192
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
South Texas Cancer Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Chimeric Therapies
Investigators
Study Chair: James N. Lowder, MD Chimeric Therapies
More Information
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ClinicalTrials.gov Identifier: NCT00004255     History of Changes
Other Study ID Numbers: CHIMERIC-HM01
CDR0000067502 ( Registry Identifier: PDQ (Physician Data Query) )
WSU-10-02-99-M01-FB
First Posted: May 9, 2003    Key Record Dates
Last Update Posted: July 10, 2013
Last Verified: February 2002

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
 childhood acute lymphoblastic leukemia in remission
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Graft vs Host Disease
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
Cyclophosphamide
Tacrolimus
 Fludarabine phosphate
Antilymphocyte Serum
Fludarabine
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating