ASCT0631:Phase III Randomized Study of Filgrastim (G-CSF)-Stimulated Allogeneic Bone Marrow Transplantation Versus Conventional Bone Marrow Transplantation in Pediatric Patients With Hematologic Cancer or Other Diseases
| Phase | Type | Status | Age | Sponsor |
|---|
| Phase III | Treatment | Active | Under 22 | COG |
Outline
- This is a randomized, multicenter study. Patients are stratified according to risk (high vs intermediate vs standard). Patients co-enrolled on clinical trial COG-ASCT0431 are also stratified according to study arm (arm I vs arm II).
- Conditioning regimen:
- Co-enrolled on COG-ASCT0431 or COG-AAML0531: Patients receive a conditioning regimen as defined on that treatment study.
- Acute lymphoblastic leukemia (ALL): Patients undergo total-body irradiation (TBI) twice daily on days -8 to -6. Patients receive thiotepa IV on days -5 and -4 and high-dose cyclophosphamide IV over 1 hour on days -3 and -2. Some patients with CNS leukemia or very high-risk ALL in first complete remission receive cranial radiotherapy.
- Acute myeloid leukemia, juvenile myelomonocytic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes (myeloid malignancies): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6 and high-dose cyclophosphamide IV over 1 hour on days -5 to -2.
- Graft-vs-host disease (GVHD) prophylaxis:
- Co-enrolled on COG-ASCT0431 or COG-AAML0531: Patients undergo GVHD prophylaxis as defined on that treatment study.
- ALL: Patients receive tacrolimus IV or orally beginning on day -2 and continuing until day 42, folllowed by a taper until day 98. Patients also receive methotrexate IV on days 1, 3, and 6.
- Myeloid malignancies: Patients receive cyclosporine IV continuously or orally beginning on day -1 and continuing until day 42 or day 50, followed by a taper for 8-16 weeks. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
- Allogeneic bone marrow transplantation (BMT): Patients are randomized to 1 of 2 transplantation arms.
- Arm I: Patients undergo filgrastim (G-CSF)-stimulated allogeneic BMT on day 0.
- Arm II: Patients undergo conventional allogeneic BMT on day 0.
After completion of study treatment, patients are followed at 1 year and then annually for 5-10 years.
Objectives
Primary
- Compare improvement in event-free survival of patients with hematologic cancer or other diseases undergoing filgrastim (G-CSF)-stimulated bone marrow transplantation (BMT) vs conventional BMT.
Secondary
- Compare the incidence and time to engraftment in patients treated with these regimens.
- Compare rates of acute and chronic graft-vs-host disease (GVHD) in patients treated with these regimens.
- Correlate incidence of acute and chronic GVHD with absolute T-cell numbers, Th1 vs Th2 profile of T cells, dendritic cell populations, and T-regulatory cell content.
- Assess the impact of G-CSF-stimulated BMT as a stem cell source on hospital stay and treatment-related mortality at day 100 in patients treated with this regimen.
- Compare short- and long-term toxicities of these regimens in these patients.
Projected Accrual
- A total of 425 patients will be accrued for this study.
Disease Characteristics:
- Diagnosis of hematologic cancer or other disease, including any of the following:
- Chronic myelogenous leukemia in first or second chronic phase
- Acute lymphoblastic leukemia (ALL), meeting any of the following criteria:
- Relapsed ALL enrolled on a Children's Oncology Group (COG) relapse clinical trial OR received ≥ 1 round of reinduction therapy (4-6 weeks) and 1 round of intensive consolidation chemotherapy (3-6 weeks)
- ALL in second complete remission (CR)* after a bone marrow, extramedullary, or combined bone marrow and extramedullary relapse
- Very high-risk ALL in first CR, defined as any of the following:
- Philadelphia chromosome-positive ALL
- Hypodiploidy (< 44 chromosomes)
- Mixed lineage leukemia rearrangement
- Induction failure
- Acute myeloid leukemia in first or second CR
- Induction therapy must be completed
- Juvenile myelomonocytic leukemia
- Myelodysplastic syndromes
- Note: *As evidenced by M1 bone marrow and < 5% blasts by morphology]
- No clinically evident CNS or extramedullary disease
- No blasts seen on cerebrospinal fluid cytospin
- Post-relapse reinduction therapy must be completed
- Not planning to receive reduced-intensity conditioning regimen
- Not planning to receive a graft that has undergone T-cell depletion
- No Down syndrome
- Matched sibling donor must be available
- HLA-A, -B, and DRB1 identical OR 1-antigen mismatched (i.e., 5/6 or 6/6 antigen match)
Age
- Less than 22 years at time of study entry
Performance Status
- Karnofsky performance status 60-100% (patients > 16 years of age)
- Lansky PS 60-100% (patients ≤ 16 years of age)
Life Expectancy
Hematopoietic
Hepatic
- AST or ALT < 5 times upper limit of normal for age
- Bilirubin < 2.5 mg/dL (unless due to Gilbert's syndrome)
Renal
- Creatinine normal OR creatinine clearance or glomerular filtration rate ≥ 70 mL/min
Cardiovascular
- Shortening fraction ≥ 27% by echocardiogram OR LVEF ≥ 50% by radionuclide angiogram
Pulmonary
- FEV1, FVC, and DLCO ≥ 60% OR meets the following criteria (for patients unable to cooperate for pulmonary function tests):
- No evidence of dyspnea at rest
- No exercise intolerance
- No requirement for supplemental oxygen therapy
Other
- Not pregnant or nursing
- No known HIV
- No known uncontrolled fungal, bacterial, or viral infections
- Patients acquiring fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT scan
Prior/Concurrent Therapy:
- See Disease Characteristics
- No prior allogeneic or autologous stem cell transplantation
For more information, contact:
Rebecca Turner, MS, CCRP
Cincinnati Children's Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org
