Recruiting

Phase 2

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

Sponsor:

Pediatric Transplantation & Cellular Therapy Consortium

Code:

NCT03509961

Conditions

B-cell Acute Lymphoblastic Leukemia

Eligibility Criteria

Sex: All

Age: 1 - 25

Healthy Volunteers: Not accepted

Interventions

NGS-MRD

Myeloablative allogeneic HCT with a non-TBI conditioning regimen

Study Details

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

Study ID

NCT03509961

Start date

Aug 29, 2018

Status verified date

Nov, 2024

Completion date

Jul 1, 2026

Anticipated

Primary completion date

Jul 1, 2025

Anticipated

Eligibility Criteria

Sex: All

Age: 1 - 25

Healthy Volunteers: Not accepted

Inclusion Criteria for the Observational Arm:

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

Inclusion Criteria for 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.
Patients in CR1 or CR2 after blinatumomab treatment.
Patients in CR1 or CR2 after CAR-T cellular therapy.
Karnofsky Index or Lansky Play-Performance Scale ≥ 60 % on pre-transplant evaluation. Karnofsky scores must be used for patients > 16 years of age and Lansky scores for patients < 16 years of age.
Able to give informed consent if > 18 years, or with a legal guardian capable of giving informed consent if < 18 years.
Adequate organ function (within 4 weeks of initiation of preparative regimen), defined as:
Pulmonary: FEV1, FVC, and corrected DLCO must all be ≥ 50% of predicted by pulmonary function tests (PFTs). For children who are unable to perform for PFTs due to age, the criteria are: no evidence of dyspnea at rest and no need for supplemental oxygen.
Renal: Creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73 m2 or a serum creatinine based on age/gender.
Cardiac: Shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA) or ejection fraction of ≥ 50% by echocardiogram or radionuclide scan (MUGA), choice of test according to local standard of care.
Hepatic: SGOT (AST) or SGPT (ALT) < 5 x upper limit of normal (ULN) for age. Conjugated bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome.

Exclusion Criteria:

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

Enrollment

95 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Observational Arm

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.

other: Treatment Arm

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.

Interventions

NGS-MRD

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.

Myeloablative allogeneic HCT with a non-TBI conditioning regimen

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

Primary outcome measure

Two Year Event-free Survival [ Time Frame: Two years ]

Central Contacts and Locations

Central contacts

Liz Gourdine

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

Locations

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

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Lisa Beatty

(205) 638-9364 lbeatty@peds.uab.edu

Principal Investigator:

Joseph Chewning, MD

Phoenix Children's Hospital

Recruiting

Phoenix, Arizona, United States, 85016

Contacts

Desiree Tobin

dtobin@phoenixchildrens.com

Principal Investigator:

Dana Salzberg, MD

City of Hope

Recruiting

Duarte, California, United States, 91010

Contacts

Ahmed Tahoun, MBBS, MBA

626-218-4350 atahoun@coh.org

Principal Investigator:

Anna Pawlowska, MD

Children's Hospital Los Angeles

Recruiting

Los Angeles, California, United States, 90027

Contacts

Aunsha Williamson

323-361-7551 awilliamson@chla.usc.edu

Principal Investigator:

Hisham Abdel-Azim, MD

UCLA Mattel Children's Hospital

Recruiting

Los Angeles, California, United States, 90095

Contacts

Andres Vargas

(310) 825-6742 AndresVargas@mednet.ucla.edu

Principal Investigator:

Ted Moore, MD

UCSF Benioff Children's Hospital Oakland

Recruiting

Oakland, California, United States, 94609

Contacts

Julia Klein

510-597-7169 jklein@mail.cho.org

Principal Investigator:

nahal Lalefar, MD

UCSF

Recruiting

San Francisco, California, United States, 94123

Contacts

Kevin Magruder

415-476-3834 Kevin.Magruder@ucsf.edu

Principal Investigator:

Christine Higham, MD

Children's Hospital Colorado

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Marguerite Dyer

720-777-5230 marguerite.dyer@childrenscolorado.org

Principal Investigator:

Amy Keating, MD

Yale University School of Medicine

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Linda Eford

203-737-6219 Linda.eford@yale.edu

Principal Investigator:

Niketa Shah, MD

Alfred I. duPont Hospital for Children - Nemours Deleware

Recruiting

Wilmington, Delaware, United States, 19803

Contacts

Ande Wrightson

302-651-5584 Andrea.Wrightson@nemours.org

Principal Investigator:

Emi Caywood, MD

University of Florida

Recruiting

Gainesville, Florida, United States, 32610

Contacts

Beate Greer

bgreer01@ufl.edu

Principal Investigator:

Biljana Horn, MD

Nicklaus Children's Hospital

Recruiting

Miami, Florida, United States, 33155

Contacts

Guido Elias

786-624-3513 Guido.Elias@Nicklaushealth.org

Principal Investigator:

Jorge Galvez, MD

Johns Hopkins All Children's Hospital

Recruiting

Saint Petersburg, Florida, United States, 33701

Contacts

Kelsey Titus

727-767-3229 Ktitus2@jhmi.edu

Principal Investigator:

Benjamin Shrine, MD

Children's Healthcare of Atlanta

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Judson Russell

Judson.Russell@choa.org

Principal Investigator:

Muna Qayed, MD

Riley Hospital for Children - Indiana University

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Courtney Spiegel

317-948-0581 clorch@iu.edu

Principal Investigator:

Jodi Skiles, MD

Floating Hospital for Children at Tufts Medical Center

Recruiting

Boston, Massachusetts, United States, 02111

Contacts

Jaime Chisholm

jchisholm1@tuftsmedicalcenter.org

Principal Investigator:

Jason Law, MD

Dana Faber Cancer Institute/ Boston Children's Hospital

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Andrea DeMarsh

617-632-3483 Andrea_Demarsh@dfci.harvard.edu

Principal Investigator:

Steven Margossian, MD

Helen DeVos Children's Hospital at Spectrum Health

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Laura Paulsen

616.391.5075 Laura.Paulsen@spectrumhealth.org

Principal Investigator:

Ulrich Duffner, MD

Children's Mercy Hospital

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Katrina Walters

(816) 302-6894 kdwalters@cmh.edu

Principal Investigator:

Ibrahim Ahmed, MD

Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601

Contacts

Elana Smilow

551-996-5673 Elana.smilow@hackensackmeridian.org

Principal Investigator:

Jennifer Krajewski, MD

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Contacts

Patti Brucato

716-845-8968 Patti.Brucato@RoswellPark.org

Principal Investigator:

Barbara Bambach, MD

Atrium Health - Levine Cancer Center

Recruiting

Charlotte, North Carolina, United States, 28203

Contacts

Tracey Fukes

980-442-2310 Tracy.Fukes@atriumhealth.org

Principal Investigator:

Jeffrey Huo, MD

The University of Texas M. D. Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Sherry Melton

713-745-1473 sjmelton@mdanderson.org

Principal Investigator:

Kris Mahadeo, MD

Methodist Healthcare System

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Candace Taylor

210-575-7379 Candace.taylor@mhshealth.com

Principal Investigator:

Troy Quigg, DO

More Information

Sponsor

Pediatric Transplantation & Cellular Therapy Consortium

Last update posted

May 4, 2025

Last verified

Nov, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Pediatric Transplantation & Cellular Therapy Consortium on 2025-05-04.