The EndRAD Trial: Eliminating Total Body Irradiation (TBI) for NGS-MRD Negative Children, Adolescents, and Young Adults With B-ALL

NCT03509961 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CHLA-18-00141
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 24

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).

Conditions

B-cell Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Two Year Event-free Survival

  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.

  Two years

Study Arms (2)

Observational Arm

OTHER

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.

Diagnostic Test: NGS-MRD

Treatment Arm

OTHER

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.

Diagnostic Test: NGS-MRD; Drug: Myeloablative allogeneic HCT with a non-TBI conditioning regimen

Interventions

NGS-MRD DIAGNOSTIC_TEST

Next generation sequencing minimal residual disease (NGS-MRD) is a test that has increased sensitivity over multichannel flow cytometry to better identify risk of key outcomes after HCT. Patients that have a pre-HCT negative NGS-MRD results may be eligible to proceed to the treatment arm of the study that uses a non-TBI conditioning regimen.

Observational Arm; Treatment Arm

Myeloablative allogeneic HCT with a non-TBI conditioning regimen DRUG

Myeloablative study regimen will consist of busulfan, fludarabine and thiotepa. day -7: Fludarabine and Busulfan day -6: Fludarabine and Busulfan day -5: Fludarabine and Busulfan day -4: Fludarabine and Busulfan day -3: Fludarabine day -2: Thiotepa day -1: Rest Day 0: Transplant

Treatment Arm

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Any patient with ALL who undergoes Myeloablative HCT including any of the following:
• Patients who are pre-HCT NGS-MRD positive.
• Patients \<1 year old who are pre-HCT NGS-MRD negative.
• Patients who are pre-HCT NGS-MRD negative (CR1/CR2) who received inotuzumab ozogamicin therapy before proceeding to HCT.
• Patients who are pre-HCT NGS-MRD negative and will be receiving haploidentical HCT.
• Patients who are pre-HCT NGS-MRD negative in CR2 with history of CNS relapse.
• Patients who have received blinatumomab, but are \>CR2 prior to HCT.
• Patients who have received CART-T cellular therapy, but are \>CR2 prior to HCT.
• Patients with pre-HCT NGS-MRD negative in ≥ CR3.
• Any T-ALL and MPAL patients undergoing first allogeneic HCT
• Any patient who is pre-HCT NGS-MRD negative and eligible for participation in the treatment arm but family does not consent for treatment arm or treating physician believe it is in the patient best interest not to enroll on the treatment arm
• Pre-HCT NGS-MRD negative
• Age ≥ 1 year and ≤ 25 years
• Disease status: B-ALL in first (CR1) or second remission (CR2)
• No prior allogeneic hematopoietic stem cell transplant.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pediatric Transplantation & Cellular Therapy Consortium: lead

Study Sites (24)

Children's of Alabama/University of Alabama in Birmingham(UAB)

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

UCLA Mattel Children's Hospital

Los Angeles, California, 90095, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

UCSF

San Francisco, California, 94123, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

RECRUITING

Alfred I. duPont Hospital for Children - Nemours Deleware

Wilmington, Delaware, 19803, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Dana Faber Cancer Institute/ Boston Children's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Atrium Health - Levine Cancer Center

Charlotte, North Carolina, 28203, United States

RECRUITING

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Methodist Healthcare System

San Antonio, Texas, 78229, United States

RECRUITING

Related Publications (1)

• Andolina JR, Fries C, Boulware R, Vargas A, Fraint E, Barth M, Ambrusko S, Comito M, Monteleone P. Successful Bone Marrow Transplantation With Intensive Post-transplant Intrathecal Chemotherapy for CNS Relapsed AML in 2 Infants. J Pediatr Hematol Oncol. 2022 Jan 1;44(1):e264-e267. doi: 10.1097/MPH.0000000000002151.

  PMID: 33843815 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Abdel-Azim Hisham, MD

  Loma Linda University

  PRINCIPAL INVESTIGATOR

• Troy Quigg, DO, MS

  Helen DeVos Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liz Gourdine

CONTACT

323-361-6652; EndRAD@chla.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: April 27, 2018
• Study Start: August 29, 2018
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 4, 2025

Record last verified: 2024-11

Locations

US (24)