CART Therapy for B-Cell Acute Lymphoblastic Leukemia
A Multicenter 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 Lymph...
Recruiting
N/AInterventional Study
B-AllAcute Lymphoblastic Leukemia
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
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Review the details below, then apply to join this clinical trial.
At a Glance
Age
1 – 25
Sex
Any
Study type
Interventional
Purpose
Diagnostic
Participants needed
60 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Who this trial is looking for
This trial is looking for children and young adults with B-cell acute lymphoblastic leukemia who have received CART therapy recently. Participants will visit the clinic every two weeks for blood and bone marrow tests to check for signs of cancer relapse.
Are You a Good Fit for This Trial?
You may be able to join if
I am between 1 and 25 years old.
I have been diagnosed with B-Cell Acute Lymphoblastic Leukemia.
I have received CART therapy within the last 42 days.
I have no measurable blood cancer cells.
I am in complete remission 42 days after CART therapy.
I have an allogeneic stem cell transplant donor identified.
I have low B-cell levels after CART therapy.
You may not be able to join if
I have had a stem cell transplant before.
I have active disease that requires ongoing imaging.
I have active brain disease that needs treatment.
I have serious health issues that would prevent a stem cell transplant.
I have an uncontrolled illness that would affect my ability to follow the study.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
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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 b…
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 2 years.
Trial Locations
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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…
* 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.
* Are NGS MRD negative by tracking sample in the bone marrow within 42 days post CD19 CART infusion confirmed by NGS MRD testing.
* Received first CD19 (4-1BB) CART within 42 days prior to enrollment. 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 42 days post CD19 CART infusion. 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.
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