The EndRAD Trial: Eliminating Total Body Irradiation (TBI) for NGS-MRD Negative Children, Adolescents, and Young Adults With B-ALL
- Conditions
- B-cell Acute Lymphoblastic Leukemia
- Interventions
- Diagnostic Test: NGS-MRDDrug: Myeloablative allogeneic HCT with a non-TBI conditioning regimen
- Registration Number
- NCT03509961
- Brief Summary
This study will evaluate the use of non- TBI (total body irradiation) conditioning for B-ALL patients with low risk of relapse as defined by absence of NGS-MRD (next generation sequencing minimal residual disease) before receiving a hematopoietic cell transplant (HCT). Patients diagnosed with B-ALL who are candidates for HCT will be screened by NGS-MRD on a test of bone marrow done before the HCT. Subjects who are pre-HCT NGS-MRD negative will be eligible to receive a non-TBI conditioning regimen as part of the treatment cohort of the study. Subjects who are pre-HCT NGS-MRD positive will be treated as per treating center standard and will be followed in an observational cohort (HCT center standard of care).
- Detailed Description
A Phase II pilot trial will estimate survival after a non-TBI based conditioning regimen in patients diagnosed with B-acute lymphoblastic leukemia (ALL) who are pre-allogeneic hematopoietic cell transplantation (HCT) next-generation-sequence (NGS) minimal residual disease (MRD) negative.
The relationship of NGS-MRD status to survival in children, adolescents, and young adults with B-ALL undergoing any approach to allogeneic HCT will be explored in a larger cohort (treatment \[phase II\] and observational arms of the study).
The primary objective is to estimate 2-year event free survival (EFS) in pre-HCT NGS-MRD negative patients with B-ALL undergoing a non-TBI based conditioning regimen through a multi-center prospective trial. The accrual period is 3 years.
Patients that are NGS-MRD negative with B-ALL may be eligible for the Treatment Arm, which is myeloablative non-TBI conditioning with busulfan, fludarabine, and thiotepa followed -matched related, unrelated, and umbilical cord blood transplants. Patients that are NGS-MRD positive will be followed on the observational arm for outcome.
Study sampling will include NGS-MRD bone marrow (BM) aspirate and peripheral blood (PB) samples collected \[same day when possible\] pre-HCT (within 4 weeks), and post-HCT on days 42 ± 14, 100 ± 20, and 365 ± 60; PB samples only will also be collected day 180± 60 and 270± 60; day +30, day +100, and 1-year post-HCT. NGS-MRD peripheral blood sample only at 6 months and 9 months post-HCT; (Blast specimen at time of diagnosis or relapse is required for NGS-MRD testing).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 95
Not provided
- CR2: exclude patients with history of CNS relapse (i.e. in CR2 with history of CNS isolated or combined relapse; CNS 2 will also be considered as CNS 3 for this purpose) from the treatment arm of study (can be enrolled on the observational arm).
- Patients who have received inotuzumab treatment prior to allogeneic HCT are NOT eligible for the study treatment arm. Inotuzumab treatment may increase the risk of VOD/SOS for any allogeneic HCT recipient, but could potentiate the risk for with busulfan-based myeloablation (study-directed non-TBI conditioning). All inotuzumab-treated patients are eligible for the observational arm (HCT center standard of care).
- Patients receiving non-myeloablative conditioning are not allowed on the observational arm (reduced toxicity conditioning with Flu/Mel/Thio is allowed on the observational arm).
- Pregnant or lactating females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants.
- Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded. Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no evidence or minimal evidence of non-progressive disease remaining by CT evaluation.
- Patients with active CNS leukemia or any other active site of extramedullary disease at the time of enrollment are not permitted.
- T-ALL and MPAL patients are only allowed on the observational arm.
- Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL with known poor outcome are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm NGS-MRD Patients enrolled to the observational arm that are NGS-MRD pre-HCT are considered for the Treatment Arm. Patients will receive a myeloablative non-TBI conditioning regimen prior to the transplant consisting on busulfan, fludarabine and thiotepa. Patients will be followed for outcome for up to 5 years. Treatment Arm Myeloablative allogeneic HCT with a non-TBI conditioning regimen Patients enrolled to the observational arm that are NGS-MRD pre-HCT are considered for the Treatment Arm. Patients will receive a myeloablative non-TBI conditioning regimen prior to the transplant consisting on busulfan, fludarabine and thiotepa. Patients will be followed for outcome for up to 5 years. Observational Arm NGS-MRD Patients are enrolled to the observational arm to proceed with NGS-MRD testing pre-HCT. If NGS-MRD negative, eligible patients may be considered for the Treatment Arm to receive a myeloablative non-TBI conditioning regimen prior to HCT. If NGS-MRD positive, patients may continue in the observational arm and receive HCT under the direction of their transplant physician and followed on the study for outcome.
- Primary Outcome Measures
Name Time Method Two Year Event-free Survival Two years The primary objective of this study is the two Year Event-free Survival for patients with high-risk or recurrent B-ALL who proceed to HCT and who are NGS-MRD negative when treated with a non-TBI preparative regimen.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (24)
Children's of Alabama/University of Alabama in Birmingham(UAB)
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
UCLA Mattel Children's Hospital
🇺🇸Los Angeles, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
UCSF
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Alfred I. duPont Hospital for Children - Nemours Deleware
🇺🇸Wilmington, Delaware, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Riley Hospital for Children - Indiana University
🇺🇸Indianapolis, Indiana, United States
Floating Hospital for Children at Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Faber Cancer Institute/ Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Atrium Health - Levine Cancer Center
🇺🇸Charlotte, North Carolina, United States
The University of Texas M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Methodist Healthcare System
🇺🇸San Antonio, Texas, United States