CAR T-Cell Therapy for Acute Lymphoblastic Leukemia

Overseen By Aimee C. Talleur, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Systemic steroids, Immunosuppressives

Disqualifiers: Primary immunodeficiency, HIV, Severe infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SJCAR19, a type of CAR T-cell therapy that uses modified immune cells to combat acute lymphoblastic leukemia (ALL) that has returned or resisted other treatments. The main goals are to find the safest dose, determine how long the treatment remains in the body, check for side effects, and assess its effectiveness against cancer. It targets young patients with CD19+ ALL who have not responded to other therapies. Participants must have detectable leukemia and may have experienced multiple relapses or treatment failures. As a Phase 1, Phase 2 trial, this research aims to understand how SJCAR19 works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking cancer treatment development.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot receive certain treatments like high-dose steroids or immunosuppressive therapy shortly before the CAR T-cell infusion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the SJCAR19 treatment is usually well-tolerated by patients. In one study, participants experienced a low rate of serious side effects, suggesting the treatment might be safe. However, this remains an early stage of testing. The researchers will continue to collect safety information as more people try the treatment. Participants should discuss possible risks with their doctor before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about SJCAR19 therapy for acute lymphoblastic leukemia (ALL) because it uses a groundbreaking approach called CAR T-cell therapy. Unlike traditional treatments like chemotherapy, which generally target rapidly dividing cells, SJCAR19 harnesses the patient's own immune cells, genetically modifying them to better recognize and attack leukemia cells. This personalized and targeted method aims to offer a more precise and potentially more effective treatment, with fewer side effects compared to conventional chemotherapy. Additionally, the use of the CliniMACS System for cell preparation ensures a high-quality product, offering hope for improved outcomes in patients with ALL.

What evidence suggests that SJCAR19 therapy might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that CAR T-cell therapy, such as the SJCAR19 treatment studied in this trial, holds promise for treating CD19+ acute lymphoblastic leukemia (ALL). This therapy modifies the body's immune cells to better attack cancer cells. Early studies have found that these treatments can lead to high response rates, with many patients experiencing a reduction in cancer symptoms. The period without symptoms, known as remission, can be significant, offering hope for those with hard-to-treat leukemia. Although this is an early study, the results so far suggest that SJCAR19 could effectively manage cases where leukemia has returned or is not responding to other treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Aimee C. Talleur, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young people (≤21 years old) with a specific type of leukemia called CD19+ ALL that hasn't responded to other treatments or has come back. They should have a life expectancy over 8 weeks, be able to perform certain physical activities, and not be pregnant or breastfeeding. They must agree to use birth control and can't join if they have severe infections, HIV, CNS-3 disease with neurological changes, are on high-dose steroids or immunosuppressants.

Inclusion Criteria

I am 21 years old or younger.

You have a type of leukemia called CD19+ ALL and have one or more of the following: your cancer has not responded to at least two rounds of chemotherapy, your cancer has not responded to additional treatment after previous attempts, your cancer has relapsed multiple times, you have relapsed after a bone marrow transplant, you need a bone marrow transplant but are not eligible, you are under 21 years old, you have a good performance score, you are expected to live for at least 12 more weeks, you are eligible for or have already undergone apheresis.

CD19+ ALL with any of the following: Minimal Residual Disease (MRD) ≥ 1% at end of up-front induction therapy, Hypodiploid (< 44 chromosomes or < 0.95 DNA index) CD19+ ALL with detectable disease at the end of up-front induction therapy, Increase in disease burden any time after the completion of up-front induction therapy, Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission, Refractory disease despite salvage therapy, 1st or greater relapse, Estimated life expectancy of > 12 weeks, Karnofsky or Lansky (age-dependent) performance score ≥ 50, Patients with a history of prior allogeneic hematopoietic cell transplantation [HCT] must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis

Exclusion Criteria

You have had allergic reactions to products that contain murine protein in the past.

You have a condition that weakens your immune system.

My cancer has spread to my brain, with or without symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Manufacturing

Participants undergo autologous apheresis and manufacturing of the SJCAR19 product

3-4 weeks

Lymphodepleting Chemotherapy

Participants receive a lymphodepleting chemotherapy regimen of fludarabine and cyclophosphamide, followed by Mesna

1 week

Treatment

Participants receive a single infusion of the SJCAR19 cellular product

1 day

Follow-up

Participants are monitored for safety, maximum tolerated dose, dose-limiting toxicities, and complete response rate

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SJCAR19 product

Trial Overview The study tests CAR T-cell therapy using engineered immune cells (SJCAR19 product) in children and young adults with relapsed/refractory leukemia. It aims to find the highest safe dose, how long these cells last in the body, their side effects, and effectiveness against this type of leukemia.

How Is the Trial Designed?

Group I: SJCAR19 Therapy Experimental Treatment 5 Interventions

Patients in both the Phase I and Phase II portion of the study will receive lymphodepleting chemotherapy (unless determined by PI that lymphodepletion is not necessary), followed by a single infusion of the patient-derived SJCAR19 cellular product. The most commonly used lymphodepleting chemotherapy regimen will consist of the agents: Fludarabine and Cyclophosphamide. They will also receive Mesna. Dosing of SJCAR19 on the Phase I study will follow a dose escalation schema, with dose changes based on dose-limiting toxicities. In the Phase II study, SJCAR19 dosing with follow the maximum tolerated dose, as determined in the Phase I portion. Cells for infusion are prepared using the CliniMACS System.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

Anti-CD19 CAR T-cell therapy has shown high response rates in treating relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), but many patients experience relapse due to the therapy's limited persistence and tumor escape mechanisms.

The review highlights new CAR targets and strategies to enhance CAR T-cell effectiveness while also addressing serious side effects like cytokine release syndrome and neurotoxicity, aiming to improve patient outcomes in R/R B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19. Acharya, L., Garg, A., Rai, M., et al.[2023]

An 11-year-old girl with relapsed acute B lymphoblastic leukemia (B-ALL) was treated with fourth generation CD19 CAR-T therapy, which was found to be effective and safe, resulting in a negative minimal residual disease after treatment.

Despite initial success and 10 months of disease-free survival, the patient ultimately relapsed due to increasing TEL-AML1 gene copies, highlighting the need for ongoing monitoring and potential further interventions in CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review]. Zuo, Y., Wang, J., Lu, A., et al.[2020]

CAR T cell therapy, specifically targeting the CD19 antigen, has shown high response rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), indicating its potential as a new treatment option.

Despite its effectiveness, CAR T cell therapy is associated with severe toxicities like cytokine release syndrome and neurotoxicity, which pose challenges for its widespread use and highlight the need for ongoing improvements in the technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Luskin, MR., DeAngelo, DJ.[2018]

CD19-specific CAR T-cell therapy shows high initial remission rates (over 80%) in pediatric patients with relapsed or refractory B-ALL, but only 40% to 50% achieve durable remission.

The review discusses the potential benefits of consolidative hematopoietic cell transplantation for patients who achieve a complete response after CAR T-cell therapy, as well as strategies to enhance the effectiveness and longevity of CAR T cells in preventing relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing relapse after CD19 CAR T-cell therapy for pediatric ALL: the role of transplant and enhanced CAR T cells. Talleur, AC., Naik, S., Gottschalk, S.[2023]

In a phase 1 trial of 53 adults with relapsed B-cell acute lymphoblastic leukemia, 83% achieved complete remission after receiving CD19-specific CAR T cells, indicating high initial efficacy.

Patients with a low disease burden before treatment experienced significantly longer overall survival (20.1 months) and fewer severe side effects, such as cytokine release syndrome, compared to those with a higher disease burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. Park, JH., Rivière, I., Gonen, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03573700

Evaluation of CD19-Specific CAR Engineered Autologous ... SJCAR19 is a research study seeking to evaluate the use of chimeric antigen receptor (CAR) T cell therapy, a type of cellular therapy, for the treatment of ...

2. stjude.org stjude.org/care-treatment/clinical-trials/sjcar19-acute-lymphoblastic-leukemia.html

SJCAR19: CAR T-Cell Therapy for Children and Young ... SJCAR19 is a research study that tests how well a type of immunotherapy works to treat relapsed/refractory ALL in patients younger than 21 years old.

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/00/NCT03573700/Prot_SAP_004.pdf

A Phase I/II Study Evaluating SJCAR19 (CD19-Specific CAR 65. This is the first clinical study evaluating the safety and efficacy of this CAR construct for the treatment of pediatric relapsed or refractory CD19+ ALL, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11022988/

Efficacy and safety of CD19-specific CAR T cell–based ... Our results suggest that CD19-specific CAR T cell–based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S247395292500388X

Age-adjusted dosing of fludarabine for lymphodepletion in ... Higher FLU systemic exposure is associated with lower relapse risk and improved leukemia-free survival in pediatric patients with acute lymphoblastic leukemia ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9647829/

Preferential expansion of CD8+ CD19-CAR T cells ... Here we report the outcome of the phase 1 study participants (n = 12). Treatment was well tolerated, with a low incidence of both cytokine ...

7. ashpublications.org ashpublications.org/bloodadvances/article/9/18/4676/546047/Age-adjusted-dosing-of-fludarabine-for

Age-adjusted dosing of fludarabine for lymphodepletion in ... This study shows that age-based FLU dosing can increase the number of individuals within a predefined cumulative area under the curve range.