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B-cell Acute Lymphoblastic LeukemiaPhase 2NCT03509961

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

A Phase 2 study testing NGS-MRD and Myeloablative allogeneic HCT with a non-TBI conditioning regimen in people with B-cell Acute Lymphoblastic Leukemia, run by Pediatric Transplantation & Cellular Therapy Consortium at 24 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 1 year to 25 years
Conditions the study is for
B-cell Acute Lymphoblastic Leukemia
What is being tested?
NGS-MRD and Myeloablative allogeneic HCT with a non-TBI conditioning regimen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
24 sitesUnited States
Study dates
29 Aug 2018to 1 Jul 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 1 year to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 24Show fewer
  • 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.
  • 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.

Who cannot join

  • 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).

Trial locations and contacts

24 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Liz Gourdine contact

323-361-6652

EndRAD@chla.usc.edu

24 sites in 1 country

United States24 sites, 24 recruiting

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

    Judson Russell, Judson.Russell@choa.org

    Muna Qayed, MD

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Marguerite Dyer, 720-777-5230, marguerite.dyer@childrenscolorado.org

    Amy Keating, MD

    Recruiting

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

    Birmingham, Alabama, 35233

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

    Joseph Chewning, MD

    Recruiting

  • Floating Hospital for Children at Tufts Medical Center

    Boston, Massachusetts, 02111

    Jaime Chisholm, jchisholm1@tuftsmedicalcenter.org

    Jason Law, MD

    Recruiting

  • Dana Faber Cancer Institute/ Boston Children's Hospital

    Boston, Massachusetts, 02215

    Andrea DeMarsh, 617-632-3483, Andrea_Demarsh@dfci.harvard.edu

    Steven Margossian, MD

    Recruiting

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

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

    Barbara Bambach, MD

    Recruiting

  • Atrium Health - Levine Cancer Center

    Charlotte, North Carolina, 28203

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

    Jeffrey Huo, MD

    Recruiting

  • City of Hope

    Duarte, California, 91010

    Ahmed Tahoun, MBBS, MBA, 626-218-4350, atahoun@coh.org

    Anna Pawlowska, MD

    Recruiting

  • University of Florida

    Gainesville, Florida, 32610

    Beate Greer, bgreer01@ufl.edu

    Biljana Horn, MD

    Recruiting

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

    Laura Paulsen, 616.391.5075, Laura.Paulsen@spectrumhealth.org

    Ulrich Duffner, MD

    Recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

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

    Jennifer Krajewski, MD

    Recruiting

  • The University of Texas M. D. Anderson Cancer Center

    Houston, Texas, 77030

    Sherry Melton, 713-745-1473, sjmelton@mdanderson.org

    Kris Mahadeo, MD

    Recruiting

  • Riley Hospital for Children - Indiana University

    Indianapolis, Indiana, 46202

    Courtney Spiegel, 317-948-0581, clorch@iu.edu

    Jodi Skiles, MD

    Recruiting

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

    Katrina Walters, (816) 302-6894, kdwalters@cmh.edu

    Ibrahim Ahmed, MD

    Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

    Aunsha Williamson, 323-361-7551, awilliamson@chla.usc.edu

    Hisham Abdel-Azim, MD

    Recruiting

  • UCLA Mattel Children's Hospital

    Los Angeles, California, 90095

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

    Ted Moore, MD

    Recruiting

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

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

    Jorge Galvez, MD

    Recruiting

  • Yale University School of Medicine

    New Haven, Connecticut, 06520

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

    Niketa Shah, MD

    Recruiting

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

    Julia Klein, 510-597-7169, jklein@mail.cho.org

    nahal Lalefar, MD

    Recruiting

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

    Desiree Tobin, dtobin@phoenixchildrens.com

    Dana Salzberg, MD

    Recruiting

  • Methodist Healthcare System

    San Antonio, Texas, 78229

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

    Troy Quigg, DO

    Recruiting

  • UCSF

    San Francisco, California, 94123

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

    Christine Higham, MD

    Recruiting

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

    Kelsey Titus, 727-767-3229, Ktitus2@jhmi.edu

    Benjamin Shrine, MD

    Recruiting

  • Alfred I. duPont Hospital for Children - Nemours Deleware

    Wilmington, Delaware, 19803

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

    Emi Caywood, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Pilot Trial to Estimate Survival After a Non-total Body Irradiation (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

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).

Read the 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).

Being tested
NGS-MRD, Myeloablative allogeneic HCT with a non-TBI conditioning regimen
Medical subject headings
Burkitt Lymphoma

What participants receive

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

  • NGS-MRDDiagnostic 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.

  • Myeloablative allogeneic HCT with a non-TBI conditioning regimenDrug

    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

Study groups in NCT03509961
Study groupRoleWhat they receive
Observational ArmOtherPatients 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.
Receives: Diagnostic Test: NGS-MRD
Treatment ArmOtherPatients 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.
Receives: Diagnostic Test: NGS-MRD; Drug: Myeloablative allogeneic HCT with a non-TBI conditioning regimen

What is being measured

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

  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.

    Measured: Two years

Timeline

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

  1. First posted27 Apr 2018
  2. Study start29 Aug 2018
  3. Primary completion1 Jul 2025 (estimated)
  4. Study completion1 Jul 2026 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03509961
Sponsor's protocol ID
CHLA-18-00141
Status last verified
Nov 2024
First submitted
19 Mar 2018
Last updated
4 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 33843815

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NGS-MRD and Myeloablative allogeneic HCT with a non-TBI conditioning regimen in people with B-cell Acute Lymphoblastic Leukemia, run by Pediatric Transplantation & Cellular Therapy Consortium at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Liz Gourdine (323-361-6652, EndRAD@chla.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Two Year Event-free Survival (time frame: Two years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03509961, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.

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