Trial Title:
A Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymphoblastic Leu...
NCT ID:
NCT05621291
Condition:
B-All
Acute Lymphoblastic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Conditions: Keywords:
B-All
Car-Cure
Result Monitoring
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
NGS testing
Description:
antigen immunophenotype agnostic approach for disease detection using blood and bone
marrow samples
Arm group label:
1/Intervention
Summary:
Background:
Chimeric antigen receptor T-cell (CART) therapy is a form of immunotherapy which can be
used to treat people with relapsed B-ALL. For those who achieve remission after CART
alone, it may cure up to 50% of people who receive this therapy. However, for people who
relapse after CART, it can be hard to achieve remission again. In patients where CART
fails, stem cell transplant (HCT) can be used to prevent relapse and achieve cure. But
HCT can cause serious side effects. Better testing is needed to distinguish people who
can be cured with CART alone from people who may also need to have HCT.
Objective:
To see if the use of a series of blood and bone marrow tests at regular intervals can
help monitor for B-ALL relapse after CART therapy.
Eligibility:
People aged 1 to 25 years with B-ALL who have had CART therapy within the past 42 days.
They must never have had a blood stem cell transplant; they must also have no measurable
blood cancer cells.
Design:
Participants will visit the clinic every 2 weeks starting 42 days after they receive CART
therapy. Each visit will be about the same amount of time as a regular clinic visit.
about 8 hours.
Participants will have blood drawn for testing on each visit.
Bone marrow biopsy/aspirate will be done during 4 of the visits at routine timepoints
after CART. A needle will be inserted to draw a sample of tissue from inside the bone in
the hip.
A small amount of blood and tissue will be tested with ClonoSEQ and to evaluate for
normal B-cells side by side with the standard tests.
The combined testing may help determine whether participants are eligible for HCT and/or
at risk of relapse after CART.
Participants will be in the study for 1 year
Detailed description:
Background:
- Given the dismal outcomes for patients who experience a relapse following CD19 CART
and the potential for using Hematopoietic cell transplantation (HCT) for post-CART
remission consolidation for relapse prevention, there is a clear opportunity to
improve outcomes for patients with B-ALL who proceed to CART. With a goal of
improving overall survival, it remains critically important to be able to predict
which patients are at high risk of relapse in whom an HCT would be indicated for
remission consolidation. Distinguishing this high-risk cohort from low-risk patients
who are able to maintain durable remission following CART and in whom HCT-associated
toxicities could be avoided is equally important.
- Thus, in the context of this biomarker-based study, we propose a systematic approach
utilizing the best-known biomarkers for remission monitoring which assess both
functional CART persistence and incorporates antigen immunophenotype agnostic
approach for disease detection will improve LFS post CD19 CART.
Objective:
-To assess efficacy of a novel biomarker-guided risk-based strategy to monitor remission,
both by assessing functional CART persistence and incorporating antigen immunophenotype
agnostic approach (NGS monitoring) for disease detection, to inform decisions regarding
post-CART HCT needed intervention, and to successfully collect biomarker samples at the
scheduled times in enrolled HCT naive B-ALL participants receiving CD19 CART.
Eligibility:
- Age >=1 year and <= 25 years old at the time of CD19 CART infusion
- Diagnosis of CD19+ B-ALL in a bone marrow morphologic complete remission and are
flow cytometry measurable residual disease (MRD) negative within 42 days post CD19
CART infusion.
- Unsupported neutrophil count > 500 cell/mm^3
- Must have an allogeneic HCT donor identified for potential HCT
- B-cell aplasia post CD19 CART persisting until the time of the first on-study
intervention
Design:
-This single-arm multicenter study will enroll pediatric and young adult participants to
evaluate the feasibility, and potential efficacy, of a risk-based, biomarker-driven,
consolidation HCT strategy following CD19 CART.
Criteria for eligibility:
Criteria:
- INCLUSION CRITERIA:
- Age >=1 year and <= 25 years old at the time of CD19 CART infusion
- Confirmed diagnosis of CD19+ B-ALL with an informative NGS clonality sample
--Have an informative NGS clonality sample for MRD assessment based on
immunoglobulin rearrangement in bone marrow or blood at any time of active disease
between diagnosis and CD19 CART infusion and any time prior to the first on-study
intervention confirmed by NGS MRD testing.
- Post-CD19 CART infusion disease status:
- Are in bone marrow morphologic complete remission and are flow cytometry
measurable residual disease (MRD) negative within 42 days post CD19 CART
infusion and within 14 days prior to the first on-study intervention.
- Are NGS MRD negative by tracking sample in the bone marrow within 42 days post
CD19 CART infusion and within 14 days prior to the first on-study intervention
confirmed by NGS MRD testing.
- Have an absolute neutrophil count (ANC) > 500 cell/mm^3 without needing growth
factor support by 42 days post CD19 CART infusion and within 4 days prior to
the first on-study intervention.
- Received first CD19 (4-1BB) CART within 42 days prior to the first on-study
intervention. Note: Eligible CART including FDA approved Kymriah (tisagenlecleucel)
infused on a treatment plan, research study, or other comparable 4-1BB based
constructs.
Study chairs will determine whether other 4-1BB CART are considered comparable.
- All participants must have an allogeneic HCT donor identified for potential HCT.
Note: Donor identification and selection will be according to institutional
practice.
- Have B-cell aplasia (BCA) post CD19 CART persisting within 14 days prior to the
first on-study intervention. Note: BCA persisting is defined as <1% B cells
lymphocytes or <50 B cells/microliter in the peripheral blood
- Performance of all screening tests prior to day 42 post CD19 CART.
- The ability of participant or parent/guardian to understand and the willingness to
sign a written consent document or participants unable to consent if they are
represented by a Legally Authorized Representative (LAR).
EXCLUSION CRITERIA:
- Prior hematopoietic stem cell transplantation (HCT)
- Recent history of the extramedullary disease (EMD) that requires ongoing
radiographic surveillance (e.g., participants with active EMD at CD19 CART infusion
that requires monitoring by imaging without the ability to more precisely assess
disease status will be ineligible). A remote history of EMD does not exclude the
participant.
- Active and/or residual central nervous system (CNS) disease that requires ongoing
therapy or monitoring.
- Co-morbidities precluding myeloablative HCT. Note: Determination of co-morbidities
precluding myeloablative HCT will be made by the treating transplant (HCT) physician
and documented in the research record. This does not require that the participant is
immediately fully eligible for HCT, only that there are no long-term comorbidities
that would preclude a myeloablative approach (e.g., renal failure, severe cardiac
failure, long-term oxygen requirement).
- Uncontrolled, symptomatic, intercurrent illness or social situations that would
limit compliance with study requirements. Note: Determination of uncontrolled,
symptomatic illness or social situation that would limit compliance with the study
requirements will be made by the site-PI and documented in the research record.
Gender:
All
Minimum age:
1 Year
Maximum age:
25 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital of Los Angeles
Address:
City:
Los Angeles
Zip:
90027
Country:
United States
Status:
Recruiting
Contact:
Last name:
Emily Hsieh, M.D.
Phone:
Not Listed
Email:
ehsieh@chla.usc.edu
Facility:
Name:
Children's National Medical Center
Address:
City:
Washington
Zip:
20010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anant Vatsayan, M.D.
Phone:
202-476-2051
Email:
avatsayan@childrensnational.org
Facility:
Name:
Children's Healthcare of Atlanta
Address:
City:
Atlanta
Zip:
30329
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Allie Suessman
Phone:
404-712-4822
Email:
asuessm@emory.edu
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
Phone:
888-624-1937
Facility:
Name:
Dana-Farber/Boston Children s Hospital
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Mona Li
Phone:
617-632-5727
Email:
mona_li@dfci.harvard.edu
Facility:
Name:
Huntsman Cancer Institute, University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michael Pulsipher, M.D.
Phone:
801-662-4700
Email:
michael.pulsipher@hci.utah.edu
Facility:
Name:
Seattle Children's, University of Washington
Address:
City:
Seattle
Zip:
98105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Corine Summers, M.D.
Phone:
Not Listed
Email:
corinnes@uw.edu
Facility:
Name:
Fred Hutchinson Cancer Research Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cindy Hirano
Phone:
Not Listed
Email:
chirano@fredhutch.org
Start date:
November 17, 2024
Completion date:
December 31, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Institutes of Health Clinical Center (CC)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05621291
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000792-C.html
