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

    Phase 2/Phase 3
  • Study Type

  • Status

    Completed No Results Posted
  • Study Participants

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.

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 Started
Mar 31
Study Completion
May 31
Last Update
Jul 10

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



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



See Disease Characteristics
12 to 50

Performance status:

Karnofsky 70-100%

Life expectancy:

At least 12 weeks


See Disease Characteristics


Bilirubin less than 2.5 times upper limit of normal (ULN)
SGOT or SGPT less than 2.5 times ULN


Creatinine no greater than 1.5 mg/dL


LVEF greater than 50% without medication


DLCO and FVC at least 50% predicted


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


Biologic therapy:

At least 3 weeks since prior immunotherapy and recovered
At least 1 year since prior autologous transplantation
No prior allogeneic transplantation


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


See Disease Characteristics
At least 3 weeks since prior radiotherapy and recovered
No prior radiotherapy at doses that would preclude study


Not specified
No Results Posted