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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...

Primary Purpose

B-All, Acute Lymphoblastic Leukemia

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
NGS testing
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for B-All focused on measuring B-All, Car-Cure, Result Monitoring

Eligibility Criteria

1 Year - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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^3without 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.

Sites / Locations

  • Children's Hospital of Los Angeles
  • Children's National Medical Center
  • Children's Healthcare of Atlanta
  • National Institutes of Health Clinical Center
  • Dana-Farber/Boston Children s Hospital
  • Huntsman Cancer Institute, University of Utah
  • Seattle Children's, University of Washington
  • Fred Hutchinson Cancer Research Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1/Intervention

Arm Description

Systematic, frequent monitoring intervention to risk stratify pts for risk of relapse postCART

Outcomes

Primary Outcome Measures

Efficacy of novel biomarker-guided risk based strategy to monitor remission
NGS MRD testing of blood and bone marrow samples and evaluation of BCA

Secondary Outcome Measures

Time to relapse
Defined as time from CART cell infusion to relapse
Time to HCT
Defined as time from CART cell infusion to receiving HCT
Leukemia Free Survival
Defined as time from CART cell infusion to first occurrence of relapse or death
Overall survival
Defined as time from CART cell infusion to death

Full Information

First Posted
November 16, 2022
Last Updated
October 24, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05621291
Brief 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...
Official Title
A Pilot Trial to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following CAR T-cell Induced Remission in Pediatric Patients With B Lineage Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 29, 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-All, Acute Lymphoblastic Leukemia
Keywords
B-All, Car-Cure, Result Monitoring

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1/Intervention
Arm Type
Experimental
Arm Description
Systematic, frequent monitoring intervention to risk stratify pts for risk of relapse postCART
Intervention Type
Diagnostic Test
Intervention Name(s)
NGS testing
Intervention Description
antigen immunophenotype agnostic approach for disease detection using blood and bone marrow samples
Primary Outcome Measure Information:
Title
Efficacy of novel biomarker-guided risk based strategy to monitor remission
Description
NGS MRD testing of blood and bone marrow samples and evaluation of BCA
Time Frame
baseline to 1 year post CD19 CART infusion
Secondary Outcome Measure Information:
Title
Time to relapse
Description
Defined as time from CART cell infusion to relapse
Time Frame
baseline to 1 year post CD19 CART infusion
Title
Time to HCT
Description
Defined as time from CART cell infusion to receiving HCT
Time Frame
baseline to 1 year post CD19 CART infusion
Title
Leukemia Free Survival
Description
Defined as time from CART cell infusion to first occurrence of relapse or death
Time Frame
baseline to 1 year post CD19 CART infusion
Title
Overall survival
Description
Defined as time from CART cell infusion to death
Time Frame
baseline to 1 year post CD19 CART infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
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^3without 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
NCI Pediatric Leukemia, Lymphoma Transpl
Phone
(240) 760-6970
Email
ncilltct@mail.nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Nirali N Shah, M.D.
Phone
(240) 760-6970
Email
shahnn@mail.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nirali N Shah, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Hsieh, M.D.
Phone
Not Listed
Email
ehsieh@chla.usc.edu
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anant Vatsayan, M.D.
Phone
202-476-2051
Email
avatsayan@childrensnational.org
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allie Suessman
Phone
404-712-4822
Email
asuessm@emory.edu
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
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
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mona Li
Phone
617-632-5727
Email
mona_li@dfci.harvard.edu
Facility Name
Huntsman Cancer Institute, University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Pulsipher, M.D.
Phone
801-662-4700
Email
michael.pulsipher@hci.utah.edu
Facility Name
Seattle Children's, University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corine Summers, M.D.
Phone
Not Listed
Email
corinnes@uw.edu
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cindy Hirano
Phone
Not Listed
Email
chirano@fredhutch.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing will be shared with subscribers to dbGaP.
IPD Sharing Time Frame
Clinical data will be made available within 10 years after completion of the primary endpoint. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
IPD Sharing Access Criteria
Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_000792-C.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

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...

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