Childhood Acute Lymphoblastic Leukemia in RemissionPhase 3NCT00450450

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

A Phase 3 study testing allogeneic bone marrow transplantation, laboratory biomarker analysis and filgrastim in people with Childhood Acute Lymphoblastic Leukemia in Remission and Childhood Acute Myeloid Leukemia in Remission, run by Children's Oncology Group at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 21 years
Conditions the study is for: Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia
What is being tested?: allogeneic bone marrow transplantation, laboratory biomarker analysis and filgrastim
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 21 sitesUnited States
Study dates: 31 Dec 2007to 31 Mar 2022
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 21 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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:

Show all 43Show fewer

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

Who cannot join

None listed.

Trial locations and contacts

21 sites in 1 country.

City, postcode or hospital

21 sites in 1 country

United States21 sites

C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Oncology Group
Arcadia, California, 91006-3776
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287-8936
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina
Chapel Hill, North Carolina, 27599
Childrens Memorial Hospital
Chicago, Illinois, 60614
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Indiana University Medical Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
The Childrens Mercy Hospital
Kansas City, Missouri, 64108
Kosair Children's Hospital
Louisville, Kentucky, 40202
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Primary Children's Medical Center
Salt Lake City, Utah, 84113
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143
Washington University School of Medicine
St Louis, Missouri, 63110
New York Medical College
Valhalla, New York, 10595

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

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:

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.

Conditions: 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
Being tested: allogeneic bone marrow transplantation, laboratory biomarker analysis, filgrastim
Medical subject headings: Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelomonocytic, Juvenile, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

allogeneic bone marrow transplantationProcedure or surgery
Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Patients undergo allogeneic BMT
laboratory biomarker analysisOther
Correlative studies
filgrastimBiological
Also called Granulocyte Colony-Stimulating Factor, r-metHuG-CSF, G-CSF, Neupogen
Given IV

Study groups in NCT00450450
Study group	Role	What they receive
Arm I	Experimental	Patients undergo filgrastim (G-CSF)-stimulated allogeneic bone marrow transplantation on day 0. Receives: Procedure: allogeneic bone marrow transplantation; Other: laboratory biomarker analysis; Biological: filgrastim
Arm II	Active comparator	Patients undergo conventional allogeneic bone marrow transplantation on day 0. Receives: Procedure: allogeneic bone marrow transplantation; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: at 2 years

Secondary outcomes (6)

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.
Measured: Up to 10 years
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.
Measured: Up to 3 months
Estimated 100-day Transplant Related Mortality (TRM) Percentage
Death in a patient after transplant due to protocol treatment is defined as an TRM.
Measured: 100 days
Estimated Percentage of Chronic Graft-versus-host Disease (cGVHD)
cGVHD definition is based on BMT CTN MOP SEPT. 2005; outlined in Protocol Appendix III.
Measured: 18 months post-transplant
Estimated Median Time to Neutrophil Engraftment
Median Time from transplant to neutrophil engraftment
Measured: Up to 10 years
Estimated Median Length of Initial Hospitalization
Estimated and compared between randomization arms using the Wilcoxon rank-sum test.
Measured: Up to 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Dec 200731 Mar 2022

First posted22 Mar 2007 (estimated)
Study start31 Dec 2007
Primary completion1 Jun 2013
Study completion31 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Childhood Acute Lymphoblastic Leukemia in RemissionStudies of the same condition, open and under way.
More trials run by Children's Oncology GroupThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00450450
Sponsor's protocol ID: ASCT0631
Other IDs: NCI-2009-01069, COG-ASCT0631, COG-PBMTC-STC051, CDR0000532926, U10CA098543
Status last verified: Jun 2021
First submitted: 20 Mar 2007
Last updated: 28 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes