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

Primary Purpose

Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
allogeneic bone marrow transplantation
laboratory biomarker analysis
filgrastim
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Childhood Acute Lymphoblastic Leukemia in Remission

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Oncology Group
  • University of California San Francisco Medical Center-Parnassus
  • Children's Hospital Colorado
  • Childrens Memorial Hospital
  • Indiana University Medical Center
  • Riley Hospital for Children
  • Kosair Children's Hospital
  • Johns Hopkins University
  • C S Mott Children's Hospital
  • The Childrens Mercy Hospital
  • Washington University School of Medicine
  • University of Nebraska Medical Center
  • Hackensack University Medical Center
  • Roswell Park Cancer Institute
  • New York Medical College
  • University of North Carolina
  • Nationwide Children's Hospital
  • Children's Hospital of Philadelphia
  • Vanderbilt-Ingram Cancer Center
  • University of Texas Southwestern Medical Center
  • Primary Children's Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I

Arm II

Arm Description

Patients undergo filgrastim (G-CSF)-stimulated allogeneic bone marrow transplantation on day 0.

Patients undergo conventional allogeneic bone marrow transplantation on day 0.

Outcomes

Primary Outcome Measures

Estimated Two-year Event-free Survival (EFS)
EFS is defined as relapse or treatment-related mortality (TRM). relapse is defined by either morphological or cytogenetic evidence of ALL consistent with pre-transplant features.

Secondary Outcome Measures

Estimated Graft Failure Rate
Primary graft failure is defined as the failure to achieve an absolute neutrophil count of more than 5000 per cubic millimeter for at least three consecutive days by Day +42.
Estimated Incidence of Grade III-IV Acute Graft-versus-host Disease (aGVHD)
Stage III-IV aGVHD is defined as: Stage 0-3 skin, with Stage 2-3 liver, or Stage 2-3 GI; OR Stage 4 skin, liver or GI involvement.
Estimated 100-day Transplant Related Mortality (TRM) Percentage
Death in a patient after transplant due to protocol treatment is defined as an TRM.
Estimated Percentage of Chronic Graft-versus-host Disease (cGVHD)
cGVHD definition is based on BMT CTN MOP SEPT. 2005; outlined in Protocol Appendix III.
Estimated Median Time to Neutrophil Engraftment
Median Time from transplant to neutrophil engraftment
Estimated Median Length of Initial Hospitalization
Estimated and compared between randomization arms using the Wilcoxon rank-sum test.

Full Information

First Posted
March 20, 2007
Last Updated
April 1, 2022
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00450450
Brief Title
Donor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
December 31, 2007 (Actual)
Primary Completion Date
June 1, 2013 (Actual)
Study Completion Date
March 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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. 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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients undergo filgrastim (G-CSF)-stimulated allogeneic bone marrow transplantation on day 0.
Arm Title
Arm II
Arm Type
Active Comparator
Arm Description
Patients undergo conventional allogeneic bone marrow transplantation on day 0.
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Other Intervention Name(s)
bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Intervention Description
Patients undergo allogeneic BMT
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
Granulocyte Colony-Stimulating Factor, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Estimated Two-year Event-free Survival (EFS)
Description
EFS is defined as relapse or treatment-related mortality (TRM). relapse is defined by either morphological or cytogenetic evidence of ALL consistent with pre-transplant features.
Time Frame
at 2 years
Secondary Outcome Measure Information:
Title
Estimated Graft Failure Rate
Description
Primary graft failure is defined as the failure to achieve an absolute neutrophil count of more than 5000 per cubic millimeter for at least three consecutive days by Day +42.
Time Frame
Up to 10 years
Title
Estimated Incidence of Grade III-IV Acute Graft-versus-host Disease (aGVHD)
Description
Stage III-IV aGVHD is defined as: Stage 0-3 skin, with Stage 2-3 liver, or Stage 2-3 GI; OR Stage 4 skin, liver or GI involvement.
Time Frame
Up to 3 months
Title
Estimated 100-day Transplant Related Mortality (TRM) Percentage
Description
Death in a patient after transplant due to protocol treatment is defined as an TRM.
Time Frame
100 days
Title
Estimated Percentage of Chronic Graft-versus-host Disease (cGVHD)
Description
cGVHD definition is based on BMT CTN MOP SEPT. 2005; outlined in Protocol Appendix III.
Time Frame
18 months post-transplant
Title
Estimated Median Time to Neutrophil Engraftment
Description
Median Time from transplant to neutrophil engraftment
Time Frame
Up to 10 years
Title
Estimated Median Length of Initial Hospitalization
Description
Estimated and compared between randomization arms using the Wilcoxon rank-sum test.
Time Frame
Up to 10 years
Other Pre-specified Outcome Measures:
Title
Immune Reconstitution
Description
Summarized graphically. Generalized estimating equation will be used to model the levels as a function of time and randomization assignment and to test the impact of G-CSF stimulation on immune reconstruction.
Time Frame
Up to 1 year
Title
Infused Nucleated and CD34+ Cell Doses
Description
Compared using the Wilcoxon rank-sum test.
Time Frame
Up to 10 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan A. Grupp, MD PhD
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Arcadia
State/Province
California
ZIP/Postal Code
91006-3776
Country
United States
Facility Name
University of California San Francisco Medical Center-Parnassus
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Childrens Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Indiana University Medical Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Kosair Children's Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8936
Country
United States
Facility Name
C S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
The Childrens Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Primary Children's Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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