NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000792-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Recruitment has not started
Gender: Male & Female
Min Age: 1 Years
Max Age: 25 Years

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

B-All;
Car-Cure;
Result Monitoring

Recruitment Keyword(s)

None

Condition(s)

B-All;
Acute Lymphoblastic Leukemia

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Diagnostic Test: NGS testing

Supporting Site

National Cancer Institute

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

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Eligibility

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.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
10 CENTER DR
BETHESDA MD 20892
(240) 760-6970
shahnn@mail.nih.gov

NCI Pediatric Leukemia, Lymphoma Transpl
National Cancer Institute (NCI)

(240) 760-6970
ncilltct@mail.nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05621291

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NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000792-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Recruitment has not started
Gender: Male & Female
Min Age: 1 Years
Max Age: 25 Years

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

B-All;
Car-Cure;
Result Monitoring

Recruitment Keyword(s)

None

Condition(s)

B-All;
Acute Lymphoblastic Leukemia

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Diagnostic Test: NGS testing

Supporting Site

National Cancer Institute

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

--Back to Top--

Eligibility

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.


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
10 CENTER DR
BETHESDA MD 20892
(240) 760-6970
shahnn@mail.nih.gov

NCI Pediatric Leukemia, Lymphoma Transpl
National Cancer Institute (NCI)

(240) 760-6970
ncilltct@mail.nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05621291

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