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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004255
• Other study ID #: CHIMERIC-HM01
• Secondary ID: CDR0000067502WSU
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 28, 2000
• Last updated: July 9, 2013
• Start date: March 2000
• Est. completion date: May 2003

Study information

• Verified date: February 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 50 Years

Eligibility

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 Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Biological:
• anti-thymocyte globulin

• filgrastim

Drug:
• cyclophosphamide

• fludarabine phosphate

• methylprednisolone

• tacrolimus

Procedure:
• allogeneic bone marrow transplantation

• in vitro-treated bone marrow transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Presbyterian-St Luke's Medical Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	University of California San Diego Cancer Center	La Jolla	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Oregon Cancer Center	Portland	Oregon
United States	Massey Cancer Center	Richmond	Virginia
United States	University of Rochester Cancer Center	Rochester	New York
United States	South Texas Cancer Institute	San Antonio	Texas
United States	New York Medical College	Valhalla	New York
United States	Lombardi Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Chimeric Therapies

Country where clinical trial is conducted

United States,