Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Donor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Temporarily closed Under 22 NCI COG-ASCT0631 ASCT0631, COG-PBMTC-STC051, NCT00450450

Objectives

Primary

1. 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

1. Compare the incidence and time to engraftment in patients treated with these regimens.
2. Compare rates of acute and chronic graft-vs-host disease (GVHD) in patients treated with these regimens.
3. 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.
4. 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.
5. Compare short- and long-term toxicities of these regimens in these patients.

Entry Criteria

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)

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior allogeneic or autologous stem cell transplantation

Patient Characteristics:

• Karnofsky performance status (PS) 60-100% (patients > 16 years of age) OR Lansky PS 60-100% (patients ≤ 16 years of age)
• AST or ALT < 5 times upper limit of normal for age
• Bilirubin < 2.5 mg/dL (unless due to Gilbert's syndrome)
• Creatinine normal OR creatinine clearance or glomerular filtration rate ≥ 70 mL/min
• Shortening fraction ≥ 27% by echocardiogram OR LVEF ≥ 50% by radionuclide angiogram
• 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
• 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

Expected Enrollment

A total of 425 patients will be accrued for this study.

Outcomes

Event-free survival at 2 years

Engraftment kinetics
Rates of acute and chronic graft-versus-host disease
Graft characteristics, including nucleated and CD34+ cell doses and T-cell characterization
Treatment-related mortality at day 100
Length of hospital stay
Short- and long-term safety in donors

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Stephen A. Grupp, MD, PhD, Protocol chair		Ph: 215-590-2821
Haydar Frangoul, MD, Protocol co-chair		Ph: 615-936-1782; 800-811-8480 Email: haydar.frangoul@vanderbilt.edu

Related Information

PDQ® clinical trial COG-ASCT0431
PDQ® clinical trial COG-AAML0531

Registry Information
Official Title		A Phase III Randomized Trial of G-CSF Stimulated Bone Marrow vs. Conventional Bone Marrow as a Stem Cell Source in Matched Sibling Donor Transplantation
Trial Start Date		2007-12-31
Trial Completion Date		2010-05-29 (estimated)
Registered in ClinicalTrials.gov		NCT00450450
Date Submitted to PDQ		2007-01-23
Information Last Verified		2008-10-11
NCI Grant/Contract Number		CA98543