Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Supportive care, Treatment Completed 12 to 50 Other CHIMERIC-HM01 WSU-10-02-99-M01-FB, NCT00004255

Objectives

1. 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.
2. Compare the safety of these regimens in these patients.
3. Compare the disease-free survival rate at 100 days and at 6 months in patients treated with these regimens.
4. Compare the time to engraftment and percent engraftment in patients treated with these regimens.
5. Compare the reduction rate of grade II or greater acute and chronic GVHD in patients treated with these regimens.

Entry 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

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

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Chimeric Therapies Incorporated

James N. Lowder, MD, Protocol chair(Contact information may not be current)		Ph: 949-347-9640

Registry Information
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
Trial Start Date		2000-03-16
Registered in ClinicalTrials.gov		NCT00004255
Date Submitted to PDQ		2000-01-03
Information Last Verified		2002-02-25