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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


Phase 3
N/A
21 Years
Open (Enrolling)
Both
Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Juvenile Myelomonocytic Leukemia, Previously Treated Myelodysplastic Syndromes, Recurrent Childhood Acute Lymphoblastic Leukemia, Secondary Myelodysplastic Syndromes

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Trial Information

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


PRIMARY OBJECTIVE:

I. 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 OBJECTIVES:

I. Compare the incidence and time to engraftment in patients treated with these regimens.

II. Compare rates of acute and chronic graft-vs-host disease (GVHD) in patients treated with
these regimens.

III. 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.

IV. 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.

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, 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.


Inclusion Criteria:



- 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

- 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 and must be enrolled on ASCT0631D companion
study

- 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 clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
creatinine base on age and/or gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

- 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

- No prior allogeneic or autologous stem cell transplantation

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Outcome Description:

Analyzed using the stratified log-rank test.

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Stephan A. Grupp

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

ASCT0631

NCT ID:

NCT00450450

Start Date:

December 2007

Completion Date:

Related Keywords:

  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Myelodysplastic Syndromes
  • Chronic Phase Chronic Myelogenous Leukemia
  • de Novo Myelodysplastic Syndromes
  • Juvenile Myelomonocytic Leukemia
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Secondary Myelodysplastic Syndromes
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Juvenile

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Washington University School of MedicineSaint Louis, Missouri  63110
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
New York Medical CollegeValhalla, New York  10595
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Nationwide Children's HospitalColumbus, Ohio  43205-2696
University of North CarolinaChapel Hill, North Carolina  27599
Indiana University Medical CenterIndianapolis, Indiana  46202
University of Texas Southwestern Medical CenterDallas, Texas  
Childrens Memorial HospitalChicago, Illinois  60614
Children's Oncology GroupArcadia, California  91006-3776
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Riley Hospital for ChildrenIndianapolis, Indiana  46202
The Childrens Mercy HospitalKansas City, Missouri  64108
Children's Hospital ColoradoAurora, Colorado  80045
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143