Clinical trial NCT00004255: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Graft Versus Host Disease
Leukemia
Myelodysplastic Syndromes
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease
childhood myelodysplastic syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-05-09
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: Denver
country: United States
facility: Presbyterian-St Luke's Medical Center
state: Colorado
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Hospital and Clinics, University of Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Cancer Center
state: Oregon
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Cancer Institute
state: Texas
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
Study officials:
affiliation: Chimeric Therapies
name: James N. Lowder, MD
role: STUDY_CHAIR
References: