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

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

Tracking Information

• First Submitted Date: January 28, 2000
• First Posted Date: May 9, 2003
• Last Update Posted Date: July 10, 2013
• Study Start Date: March 2000
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Graft Versus Host Disease
• Leukemia
• Myelodysplastic Syndromes

Intervention

• 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

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment: Not Provided
• Original Enrollment: Not Provided
• Actual Study Completion Date: May 2003
• Primary Completion Date: Not Provided

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 50 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00004255
• Other Study ID Numbers: CHIMERIC-HM01; CDR0000067502 ( Registry Identifier: PDQ (Physician Data Query) ); WSU-10-02-99-M01-FB
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Chimeric Therapies
• Collaborators: Not Provided

Investigators

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

• PRS Account: National Cancer Institute (NCI)
• Verification Date: February 2002