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

Sponsor

Chimeric Therapies (Industry)

Overall Status

Completed

CT.gov ID

NCT00004255

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

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

Study Type:

Interventional

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 :

Mar 1, 2000

Actual Study Completion Date :

May 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
2	Presbyterian-St Luke's Medical Center	Denver	Colorado	United States	80218
3	Lombardi Cancer Center	Washington	District of Columbia	United States	20007
4	Shands Hospital and Clinics, University of Florida	Gainesville	Florida	United States	32610-100277
5	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana	United States	46202
6	James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
7	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
8	University of Rochester Cancer Center	Rochester	New York	United States	14642
9	New York Medical College	Valhalla	New York	United States	10595
10	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73190
11	Oregon Cancer Center	Portland	Oregon	United States	97201-3098
12	Hahnemann University Hospital	Philadelphia	Pennsylvania	United States	19102-1192
13	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
14	South Texas Cancer Institute	San Antonio	Texas	United States	78229
15	Massey Cancer Center	Richmond	Virginia	United States	23298-0037