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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 19-28z/IL-18 CAR T cell therapy for individuals with acute lymphoblastic leukemia (ALL), particularly if the disease has returned or resisted previous treatments. The process involves extracting a person's white blood cells, modifying them in a lab to enhance their ability to fight cancer, and then reintroducing them to the patient. The trial includes different groups, each receiving varying doses of the treatment, with some also receiving additional chemotherapy. Individuals with persistent or recurrent ALL who have previously tried specific treatment regimens might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research has shown that 19-28z/IL-18 CAR T-cell therapy has been tested in individuals with difficult-to-treat acute lymphoblastic leukemia (ALL). This therapy modifies a person's own T cells, a type of white blood cell, to enhance their ability to fight cancer.

In studies, some patients experienced side effects, but many were manageable. Common issues included fever and low blood cell counts, which doctors can often treat. While serious side effects can occur, researchers are improving management strategies.

Since this therapy remains in early testing, safety information is limited. However, similar CAR T-cell treatments for other types of leukemia have demonstrated promising safety results in studies. This suggests that while risks exist, the therapy could be safe with proper medical care. Always consult your doctor to understand the risks and benefits for your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 19-28z/IL-18 CAR T cells for treating Acute Lymphoblastic Leukemia (ALL) because they offer a novel approach by reprogramming the patient's own immune cells to target cancer. Unlike conventional chemotherapy and radiation, this treatment uses genetically engineered T cells to recognize and attack leukemia cells directly. The addition of interleukin-18 (IL-18) is particularly promising, as it may boost the immune response and enhance the effectiveness of the CAR T cells. With multiple dosing strategies, such as varying cell dosages and the inclusion of lymphodepleting chemotherapy, researchers aim to find the optimal balance between efficacy and safety.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that a new treatment, 19-28z/IL-18 CAR T cells, could effectively treat acute lymphoblastic leukemia (ALL). In past studies, similar treatments targeting the CD19 protein helped 70 to 90% of children and adults with relapsed ALL achieve complete remission, meaning no detectable cancer cells. This trial will explore different dose levels of 19-28z/IL-18 CAR T cells, which include a special protein, IL-18, to further enhance the immune system's response. Early results appear promising, but further research is needed to confirm these findings. ^{1 2 3 4 5}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4684949/

Efficacy and Toxicity Management of 19-28z CAR T Cell ... We next demonstrated potent antitumor benefit after infusing CD19-targeted 19-28z CAR T cells into five adults with relapsed or refractory B cell acute ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709919

Long-Term Follow-up of CD19 CAR Therapy in Acute ... Multiple clinical trials of CD19-specific CAR T cells have shown complete remission rates of 70 to 90% among children and adults with relapsed B ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/23-307

A Phase 1 Study of 19-28z/IL-18 CAR T Cell Therapy in ... Researchers are assessing a CAR T cell therapy to treat acute lymphoblastic leukemia (ALL) that keeps growing even with treatment.

4. nature.com nature.com/articles/s41417-021-00418-1

Use of CAR T-cell for acute lymphoblastic leukemia (ALL) ... In the follow-up studies [51] they report the dramatic ability of autologous 19–28z CAR-modified T cells to induce MRD − CRs in five patients ...

5. trial.medpath.com trial.medpath.com/clinical-trial/fda01eb121b6aee0/nct06287528-phase-1-trial-cd19-car-t-cells-all

A Study of 19-28z/IL-18 in People With Acute Lymphoblastic ... 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 ...