- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03509961
The EndRAD Trial: Eliminating Total Body Irradiation (TBI) for NGS-MRD Negative Children, Adolescents, and Young Adults With B-ALL
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
Study Overview
Status
Conditions
Intervention / Treatment
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).
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Liz Gourdine
- Phone Number: 323-361-6652
- Email: EndRAD@chla.usc.edu
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35233
- Recruiting
- Children's of Alabama/University of Alabama in Birmingham(UAB)
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Contact:
- Lisa Beatty
- Phone Number: 205-638-9364
- Email: lbeatty@peds.uab.edu
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Arizona
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Phoenix, Arizona, United States, 85016
- Recruiting
- Phoenix Children's Hospital
-
Contact:
- Desiree Tobin
- Email: dtobin@phoenixchildrens.com
-
Principal Investigator:
- Dana Salzberg, MD
-
-
California
-
Duarte, California, United States, 91010
- Recruiting
- City of Hope
-
Contact:
- Ahmed Tahoun, MBBS, MBA
- Phone Number: 626-218-4350
- Email: atahoun@coh.org
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Los Angeles, California, United States, 90027
- Recruiting
- Children's Hospital Los Angeles
-
Contact:
- Aunsha Williamson
- Phone Number: 323-361-7551
- Email: awilliamson@chla.usc.edu
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Los Angeles, California, United States, 90095
- Recruiting
- UCLA Mattel Children's Hospital
-
Principal Investigator:
- Ted Moore, MD
-
Oakland, California, United States, 94609
- Recruiting
- UCSF Benioff Children's Hospital Oakland
-
Contact:
- Julia Klein
- Phone Number: 510-597-7169
- Email: jklein@mail.cho.org
-
Principal Investigator:
- nahal Lalefar, MD
-
San Francisco, California, United States, 94123
- Recruiting
- UCSF
-
Contact:
- Kevin Magruder
- Phone Number: 415-476-3834
- Email: Kevin.Magruder@ucsf.edu
-
Principal Investigator:
- Christine Higham, MD
-
-
Colorado
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Aurora, Colorado, United States, 80045
- Recruiting
- Children's Hospital Colorado
-
Contact:
- Marguerite Dyer
- Phone Number: 720-777-5230
- Email: marguerite.dyer@childrenscolorado.org
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Principal Investigator:
- Amy Keating, MD
-
-
Connecticut
-
New Haven, Connecticut, United States, 06520
- Recruiting
- Yale University School Of Medicine
-
-
Delaware
-
Wilmington, Delaware, United States, 19803
- Recruiting
- Alfred I. duPont Hospital for Children - Nemours Deleware
-
Contact:
- Ande Wrightson
- Phone Number: 302-651-5584
- Email: Andrea.Wrightson@nemours.org
-
-
Florida
-
Gainesville, Florida, United States, 32610
- Recruiting
- University of Florida
-
Contact:
- Beate Greer
- Email: bgreer01@ufl.edu
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Miami, Florida, United States, 33155
- Recruiting
- Nicklaus Children's Hospital
-
Contact:
- Guido Elias
- Phone Number: 786-624-3513
- Email: Guido.Elias@Nicklaushealth.org
-
Principal Investigator:
- Jorge Galvez, MD
-
Saint Petersburg, Florida, United States, 33701
- Recruiting
- Johns Hopkins All Children's Hospital
-
Contact:
- Kelsey Titus
- Phone Number: 727-767-3229
- Email: ktitus2@jhmi.edu
-
Principal Investigator:
- Benjamin Shrine, MD
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Children's Healthcare of Atlanta
-
Principal Investigator:
- Muna Qayed, MD
-
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Indiana
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Indianapolis, Indiana, United States, 46202
- Recruiting
- Riley Hospital for Children - Indiana University
-
Principal Investigator:
- Jodi Skiles, MD
-
Contact:
- Courtney Spiegel
- Phone Number: 317-948-0581
- Email: clorch@iu.edu
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02111
- Recruiting
- Floating Hospital for Children at Tufts Medical Center
-
Contact:
- Jaime Chisholm
- Email: jchisholm1@tuftsmedicalcenter.org
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Principal Investigator:
- Jason Law, MD
-
Boston, Massachusetts, United States, 02215
- Recruiting
- Dana Faber Cancer Institute/ Boston Children's Hospital
-
Contact:
- Andrea DeMarsh
- Phone Number: 617-632-3483
- Email: Andrea_Demarsh@dfci.harvard.edu
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Principal Investigator:
- Steven Margossian, MD
-
-
Michigan
-
Grand Rapids, Michigan, United States, 49503
- Recruiting
- Helen DeVos Children's Hospital at Spectrum Health
-
Contact:
- Laura Paulsen
- Phone Number: 616-391-5075
- Email: Laura.Paulsen@spectrumhealth.org
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Principal Investigator:
- Ulrich Duffner, MD
-
-
Missouri
-
Kansas City, Missouri, United States, 64108
- Recruiting
- Children's Mercy Hospital
-
Contact:
- Katrina Walters
- Phone Number: 816-302-6894
- Email: kdwalters@cmh.edu
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-
New Jersey
-
Hackensack, New Jersey, United States, 07601
- Recruiting
- Hackensack University Medical Center
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Contact:
- Elana Smilow
- Phone Number: 551-996-5673
- Email: Elana.smilow@hackensackmeridian.org
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Principal Investigator:
- Jennifer Krajewski, MD
-
-
New York
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Buffalo, New York, United States, 14263
- Recruiting
- Roswell Park Cancer Institute
-
Contact:
- Patti Brucato
- Phone Number: 716-845-8968
- Email: Patti.Brucato@RoswellPark.org
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Principal Investigator:
- Barbara Bambach, MD
-
-
North Carolina
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Charlotte, North Carolina, United States, 28203
- Recruiting
- Atrium Health - Levine Cancer Center
-
Contact:
- Tracey Fukes
- Phone Number: 980-442-2310
- Email: Tracy.Fukes@atriumhealth.org
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-
Texas
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Houston, Texas, United States, 77030
- Recruiting
- The University of Texas M. D. Anderson Cancer Center
-
Contact:
- Sherry Melton
- Phone Number: 713-745-1473
- Email: sjmelton@mdanderson.org
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San Antonio, Texas, United States, 78229
- Recruiting
- Methodist Healthcare System
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Contact:
- Candace Taylor
- Phone Number: 210-575-7379
- Email: Candace.taylor@mhshealth.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
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.
|
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.
|
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 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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Two Year Event-free Survival
Time Frame: 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.
|
Two years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Hisham Abdel-Azim, MD, Children's Hospital Los Angeles
- Study Chair: Troy Quigg, DO, Methodist Hospital - Texas Transplant Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PBMTC ONC1701
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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