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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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 pediatric, adolescent and young adult patients with relapsed or refractory CD19+ acute lymphoblastic leukemia (ALL). CAR therapy combines two of the body's basic disease fighters: antibodies and T Cells. For this type of therapy, peripheral (circulating) immune cells are collected and then undergo a manufacturing process to engineer them to more effectively kill cancer cells. The SJCAR19 product will be manufactured at the St. Jude Children's Research Hospital's Good Manufacturing Practice (GMP) facility. The main purpose of this study is to determine: 1. The largest dose of SJCAR19 that is safe to give, 2. How long SJCAR19 cells last in the body, 3. The side effects of SJCAR19, and 4. Whether or not treatment with SJCAR19 is effective in treating people with refractory or relapsed ALL.

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.

What data supports the effectiveness of the treatment SJCAR19 product for Acute Lymphoblastic Leukemia?

Research shows that CAR T-cell therapy, which includes treatments like SJCAR19, has high initial response rates in patients with relapsed B-cell acute lymphoblastic leukemia (ALL). These therapies target a protein called CD19 on cancer cells, leading to significant responses, although some patients may experience relapse or side effects. ^{1 2 3 4 5}

Is CAR T-Cell Therapy safe for humans?

CAR T-Cell Therapy, including the SJCAR19 product, has shown serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), which can be life-threatening. Other potential risks include heart and lung issues, metabolic problems, and prolonged low blood cell counts. However, recent advances have improved the understanding and management of these side effects. ^{4 5 6 7 8}

How is the CAR T-cell treatment SJCAR19 unique for acute lymphoblastic leukemia?

The CAR T-cell treatment SJCAR19 is unique because it involves genetically modifying a patient's own T cells to target and attack leukemia cells by recognizing a specific marker called CD19 on their surface. This approach allows for ongoing tumor surveillance and has shown high response rates in patients who have not responded to other treatments, although it can cause serious side effects like cytokine release syndrome and neurotoxicity. ^{4 5 8 9 10}

Research Team

Aimee C. Talleur, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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.

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

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.

Exclusion Criteria

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

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

You have a condition that weakens your immune system.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. China 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]. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in the Treatment of Acute B Lymphocytic Leukemia]. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells for acute lymphoblastic leukemia. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. [2020]

8. China pubmed.ncbi.nlm.nih.gov

[Efficacy of CD19 Chimeric Antigen Receptors T Cells in the Treatment of Relapsed Patients with B Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation]. [2019]

9. United States 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. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Open access? Widening access to chimeric antigen receptor (CAR) therapy for ALL. [2022]