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

Previously Treated Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00450450
• Other study ID #: ASCT0631
• Secondary ID: NCI-2009-01069CO
• Status: Completed
• Phase: Phase 3
• Start date: December 31, 2007
• Est. completion date: March 31, 2022

Study information

• Verified date: June 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 31, 2022
• Est. primary completion date: June 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Procedure:
• allogeneic bone marrow transplantation
Patients undergo allogeneic BMT

Other:
• laboratory biomarker analysis
Correlative studies

Biological:
• filgrastim
Given IV

Locations

Country	Name	City	State
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Oncology Group	Arcadia	California
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of California San Francisco Medical Center-Parnassus	San Francisco	California
United States	New York Medical College	Valhalla	New York

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immune Reconstitution	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.	Up to 1 year
Other	Infused Nucleated and CD34+ Cell Doses	Compared using the Wilcoxon rank-sum test.	Up to 10 years
Primary	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.	at 2 years
Secondary	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.	Up to 10 years
Secondary	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.	Up to 3 months
Secondary	Estimated 100-day Transplant Related Mortality (TRM) Percentage	Death in a patient after transplant due to protocol treatment is defined as an TRM.	100 days
Secondary	Estimated Percentage of Chronic Graft-versus-host Disease (cGVHD)	cGVHD definition is based on BMT CTN MOP SEPT. 2005; outlined in Protocol Appendix III.	18 months post-transplant
Secondary	Estimated Median Time to Neutrophil Engraftment	Median Time from transplant to neutrophil engraftment	Up to 10 years
Secondary	Estimated Median Length of Initial Hospitalization	Estimated and compared between randomization arms using the Wilcoxon rank-sum test.	Up to 10 years