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

NCT ID: NCT00004255

Last Updated: 2013-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31
• Study Completion Date: 2003-05-31

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.

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.

Conditions

Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

tacrolimus

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

in vitro-treated bone marrow transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chimeric Therapies

INDUSTRY

Sponsor Role: lead

Principal Investigators

James N. Lowder, MD

Role: STUDY_CHAIR

Chimeric Therapies

Locations

University of California San Diego Cancer Center

La Jolla, California, United States

Presbyterian-St Luke's Medical Center

Denver, Colorado, United States

Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Shands Hospital and Clinics, University of Florida

Gainesville, Florida, United States

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

University of Rochester Cancer Center

Rochester, New York, United States

New York Medical College

Valhalla, New York, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oregon Cancer Center

Portland, Oregon, United States

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

South Texas Cancer Institute

San Antonio, Texas, United States

Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

Other Identifiers

CDR0000067502

Identifier Type: REGISTRY

Identifier Source: secondary_id

WSU-10-02-99-M01-FB

Identifier Type: -

Identifier Source: secondary_id

CHIMERIC-HM01

Identifier Type: -

Identifier Source: org_study_id