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

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00450450

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate and tacrolimus or cyclosporine before and after transplant may stop this from happening. It is not yet known whether donor bone marrow transplant is more effective with or without G-CSF in treating hematologic cancer or other diseases.

PURPOSE: This randomized phase III trial is studying donor bone marrow transplant with or without G-CSF to compare how well they work in treating young patients with hematologic cancer or other diseases.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Procedure: allogeneic bone marrow transplantation	Phase III

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Granulocyte colony-stimulating factor

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival at 2 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Engraftment kinetics [ Designated as safety issue: No ]
Rates of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
Graft characteristics, including nucleated and CD34+ cell doses and T-cell characterization [ Designated as safety issue: No ]
Treatment-related mortality at day 100 [ Designated as safety issue: No ]
Length of hospital stay [ Designated as safety issue: No ]
Short- and long-term safety in donors [ Designated as safety issue: Yes ]

Estimated Enrollment:	425
Study Start Date:	December 2007
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients undergo filgrastim (G-CSF)-stimulated allogeneic BMT on day 0.	Procedure: allogeneic bone marrow transplantation Patients undergo allogeneic BMT on day 0
Arm II: Active Comparator Patients undergo conventional allogeneic BMT on day 0.	Procedure: allogeneic bone marrow transplantation Patients undergo allogeneic BMT on day 0

Detailed Description:

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.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk (high vs intermediate vs standard).

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, followed 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.

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

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

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
FEV_1, 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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior allogeneic or autologous stem cell transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450450

Show 31 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Stephen A. Grupp, MD, PhD	Children's Hospital of Philadelphia
Investigator:	Haydar Frangoul, MD	Vanderbilt-Ingram Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000532926, COG-ASCT0631, COG-PBMTC-STC051
Study First Received:	March 20, 2007
Last Updated:	January 2, 2009
ClinicalTrials.gov Identifier:	NCT00450450
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

juvenile myelomonocytic leukemia
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute lymphoblastic leukemia
childhood chronic myelogenous leukemia

chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes

Study placed in the following topic categories:

Juvenile myelomonocytic leukemia
Myelodysplastic syndromes
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chronic myelogenous leukemia
Precancerous Conditions
Hematologic Neoplasms
Hematologic Diseases
Myelodysplasia
Myelodysplastic Syndromes
Acute myelogenous leukemia

Leukemia, Myeloid
Leukemia, Myelomonocytic, Juvenile
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Acute
Recurrence
Leukemia
Preleukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasm Metastasis
Bone Marrow Diseases
Acute myelocytic leukemia

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Disease
Neoplasms by Histologic Type
Syndrome

ClinicalTrials.gov processed this record on January 14, 2009