CAR T Cells for Acute Lymphoblastic Leukemia

Recruiting at 6 trial locations

Overseen By Mark Geyer, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Chemotherapy

Disqualifiers: Active malignancy, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Not specified

18 Participants Needed

Trial Summary

What is the purpose of this trial?

Participants will have a sample of their white blood cells, called T cells, collected using a procedure called leukapheresis. The collected T cells will be sent to a laboratory to be changed (modified) to become 19-28z/IL-18, the CAR T-cell therapy that participants will receive during the study. Making the participants' study therapy will take about 2-4 weeks.

Do I need to stop taking my current medications for the trial?

The trial requires stopping certain medications before participation. Steroids above 10mg daily must be stopped 7 days before leukapheresis or 72 hours before CAR T cell infusion. Chemotherapy should be stopped one week before leukapheresis or starting lymphodepleting chemotherapy, but hydroxyurea can be used up to 72 hours before these procedures.

What data supports the effectiveness of the treatment 19-28z/IL-18 CAR T cell therapy for acute lymphoblastic leukemia?

Research shows that similar CAR T cell therapies targeting CD19 have been effective in achieving remission in patients with relapsed or refractory acute lymphoblastic leukemia, with some studies reporting high initial response rates. These therapies work by genetically modifying T cells to target and destroy cancer cells, although maintaining long-term remission can be challenging. ^{1 2 3 4 5}

What safety data exists for CAR T cell therapy in treating acute lymphoblastic leukemia?

CAR T cell therapy for acute lymphoblastic leukemia has shown significant promise but is associated with some serious side effects, including cytokine release syndrome (CRS) and neurotoxicity. These side effects are generally manageable with treatments like tocilizumab (a medication that reduces inflammation) and steroids, and the therapy has been safely administered under careful monitoring. ^{3 6 7 8 9}

What makes the 19-28z/IL-18 CAR T cell treatment unique for acute lymphoblastic leukemia?

The 19-28z/IL-18 CAR T cell treatment is unique because it involves genetically engineered T cells that target specific antigens on leukemia cells, offering a novel approach for patients with relapsed or refractory acute lymphoblastic leukemia. This treatment is designed to improve the immune system's ability to fight cancer by enhancing the persistence and expansion of CAR T cells, potentially leading to better outcomes compared to traditional therapies. ^{3 4 7 10 11}

Research Team

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for people with a type of blood cancer called Acute Lymphoblastic Leukemia (ALL), specifically those who have seen their disease return. Participants must be eligible for leukapheresis, the procedure to collect white blood cells needed to create the therapy.

Inclusion Criteria

My cancer has spread to my brain or its coverings but meets certain conditions.

Signed informed consent form (ICF) prior to any study procedures

My organs are working well.

Exclusion Criteria

Patients with HIV infection

Other uncontrolled medical or psychological conditions as well as social or logistical issues

I am not currently taking steroids or have had chemotherapy recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and T-cell Modification

Participants undergo leukapheresis to collect T cells, which are then modified to become 19-28z/IL-18 CAR T cells

2-4 weeks

Treatment

Participants receive the modified 19-28z/IL-18 CAR T-cell therapy

Not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 19-28z/IL-18

Trial Overview The study involves taking participants' T cells and modifying them in a lab to become 19-28z/IL-18 CAR T cells, which are designed to fight leukemia. The process from collection to receiving the modified cells as treatment takes about 2-4 weeks.

Participant Groups

Group I: Dose Level 3 Experimental Treatment 1 Intervention

1x106 cells/kg with lymphodepleting chemotherapy (LDC)

Group II: Dose Level 2 Experimental Treatment 1 Intervention

0.5x106 cells/kg with lymphodepleting chemotherapy (LDC)

Group III: Dose Level 1 Experimental Treatment 1 Intervention

0.5x106 CAR-T cell/kg without lymphodepleting chemotherapy (LDC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a study involving five adults with relapsed B cell acute lymphoblastic leukemia (B-ALL), treatment with autologous T cells modified to express a CD19-specific CAR (19-28z) led to rapid tumor eradication and complete remissions without minimal residual disease (MRD), indicating strong efficacy of this therapy.

The treatment was generally well tolerated, although patients with higher tumor burdens experienced significant cytokine elevations, which required management with steroids, highlighting the need for monitoring and potential intervention during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Brentjens, RJ., Davila, ML., Riviere, I., et al.[2023]

Two adult patients with relapsed EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) achieved second remission after receiving tandem CD19/CD22 CAR T-cell therapy, indicating its potential efficacy for this specific leukemia subtype.

Both patients experienced manageable cytokine release syndrome but did not suffer from neurotoxicity, and they maintained remission for 14 and 13 months after undergoing hematopoietic stem cell transplantation, suggesting a promising treatment pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation. Zhang, XY., Dai, HP., Zhang, L., et al.[2021]

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]

The study found that high levels of leukemia blast contamination in the starting material did not negatively impact the manufacturing of CAR T-cells or their ability to expand, suggesting that CAR T-cell therapy can be safely produced even from contaminated samples.

Using a specific CAR design with a short linker (CAR.CD19 SL) enhances the ability of CAR T-cells to target and kill CD19+ leukemia cells, providing a potential safety advantage in preventing leukemic relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. Quintarelli, C., Guercio, M., Manni, S., et al.[2022]

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]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

In a Phase I clinical trial, 19-28z CAR T-cell therapy achieved an impressive 88% complete remission rate in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), demonstrating its efficacy as a treatment option.

While the therapy can lead to severe cytokine release syndrome (sCRS), it can be effectively managed with tocilizumab without compromising the treatment's benefits, unlike high-dose steroids which can negate the positive effects of CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer CARtography: charting out a new approach to cancer immunotherapy. Patel, JM., Dale, GA., Vartabedian, VF., et al.[2021]

In a phase 1 trial involving 45 children and young adults with relapsed or refractory B-lineage acute lymphoblastic leukemia, a defined CD19 CAR T cell product achieved an impressive 89% rate of minimal residual disease-negative (MRD-) remission, indicating strong efficacy.

The trial demonstrated a favorable safety profile, with no deaths or severe toxicities like cerebral edema, although 23% of patients experienced reversible severe cytokine release syndrome or neurotoxicity, suggesting manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Gardner, RA., Finney, O., Annesley, C., et al.[2022]

CD19CAR-T cell therapy is effective in treating relapsed and refractory B-lineage acute lymphoblastic leukemia, with four out of five patients achieving complete remission and minimal residual disease negativity.

The therapy can be safely administered with real-time monitoring of a 6-cytokine pattern, allowing for effective management of side effects like cytokine release syndrome and neurotoxicity using tocilizumab and steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. Shen, D., Song, H., Xu, X., et al.[2021]

CAR-T cell therapy targeting CD19 has been FDA-approved for treating relapsed and refractory acute lymphoblastic leukemia (ALL) in children and young adults, showing promising efficacy.

Recent trials with CD22-directed CAR-T cells indicate they can also effectively target leukemia, providing a potential alternative to CD19 therapy, although challenges like toxicity management and relapse rates remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. Pehlivan, KC., Duncan, BB., Lee, DW.[2019]

In a phase 1b/2 study involving 21 patients with relapsed and refractory acute lymphoblastic leukemia (R/R ALL), autologous CD19 CAR T cell therapy achieved a remarkable remission rate of 90%, including successful treatment of extramedullary leukemic sites.

While 16 patients experienced cytokine release syndrome and 11 had neurotoxicity, there were no toxic deaths, indicating that the treatment is relatively safe despite these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. Jacoby, E., Bielorai, B., Avigdor, A., et al.[2019]

References

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

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. [2022]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). [2020]

7. England pubmed.ncbi.nlm.nih.gov

Cancer CARtography: charting out a new approach to cancer immunotherapy. [2021]

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

Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. [2021]

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

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. [2019]

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

Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. [2019]