CAR-T Cell Therapy + IL-2 for Blood Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Synthekine

Disqualifiers: Prior CD19 therapy, Recent transplants, GVHD, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment CAR-T Cell Therapy + IL-2 for Blood Cancer?

Research shows that CAR-T cell therapy targeting CD19 is effective in treating certain blood cancers like B-cell acute lymphoblastic leukemia (B-ALL), with many patients achieving complete remission. Additionally, CAR-T cells have shown promise in treating other blood cancers, suggesting potential effectiveness for the treatment in question. ^{1 2 3 4 5}

Is CAR-T Cell Therapy safe for treating blood cancer?

CAR-T Cell Therapy has been generally safe in clinical trials for blood cancers, with some patients experiencing mild to moderate side effects like cytokine release syndrome (a reaction that can cause fever and low blood pressure) and neurotoxicity (affecting the nervous system). Serious adverse events were rare, and the treatment was well tolerated in most cases. ^{1 6 7 8 9}

How is the treatment SYNCAR-001 + IL-2 for blood cancer different from other treatments?

SYNCAR-001 is a unique treatment because it combines CAR-T cell therapy, which uses modified T cells to target and destroy cancer cells, with IL-2, a substance that can boost the immune system. This combination aims to enhance the effectiveness of the CAR-T cells in fighting blood cancer. ^{1 4 10 11 12}

Eligibility Criteria

This trial is for people with certain blood cancers like lymphoma or leukemia that have come back or didn't respond to treatment. They must have cancer cells likely to carry CD19, no brain disease symptoms, and can't have had recent bone marrow transplants or previous CD19-targeted therapies.

Inclusion Criteria

My cancer has returned or didn't respond to treatment, and it's a type of blood cancer like CLL or certain NHLs.

I don't have brain or spinal cord disease symptoms, confirmed by an MRI.

My cancer is likely to or has shown CD19 expression.

Exclusion Criteria

I had a stem cell transplant from a donor within the last 6 months.

I had a stem cell transplant using my own cells within the last 6 weeks.

I have graft-versus-host disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single fixed dose of SYNCAR-001 CAR-T intravenously in combination with repeated doses of STK-009 subcutaneously, with dose escalation and expansion phases

Up to 28 days post infusion

Follow-up

Participants are monitored for safety, tolerability, and effectiveness, including adverse events and response rates

Up to 24 months post infusion

Treatment Details

Interventions

• STK-009 (Cytokine)
• SYNCAR-001 (CAR T-cell Therapy)

Trial Overview The study tests a new therapy combining SYNCAR-001 (a type of CAR-T cell therapy) with STK-009 (an IL-2 treatment), alongside standard drugs Cyclophosphamide and Fludarabine. It's the first time this combination is being tried in humans.

Participant Groups

Group I: SYNCAR-001 + STK-009 Cohort B Experimental Treatment 2 Interventions

Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with repeated sequential ascending doses of STK-009 subcutaneously (SC) Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with repeated doses of STK-009 SC at the RP2D

Group II: SYNCAR-001 + STK-009 Cohort A Experimental Treatment 4 Interventions

Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with repeated sequential ascending doses of STK-009 subcutaneously (SC) Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with repeated doses of STK-009 SC at the RP2D

Who Is Running the Clinical Trial?

Synthekine

Lead Sponsor

Trials

3

Recruited

290+

Findings from Research

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

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]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

CAR T cell therapy, particularly targeting B cell maturation antigen (BCMA), has shown promising efficacy in early clinical trials for treating multiple myeloma, indicating its potential as a new treatment option.

Recent research has also demonstrated that CAR T cells targeting activated integrin β7 can effectively eliminate multiple myeloma cells, including specific B cell types, and preparations for a clinical trial are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. Hasegawa, K., Hosen, N.[2020]

In a study of 47 patients with relapsed/refractory large B cell lymphomas receiving CAR T-cell therapy, changes in PET scan results at 30 days post-infusion were found to be predictive of patient outcomes, with a significant correlation between SUVmean variation and progression-free survival.

Patients with a Deauville score of 4-5 and a decrease in SUVmean had a similar 1-year progression-free survival rate (61-62%) as those with a better score (1-3), while those with an increase in SUVmean had a much poorer survival rate of 33%, highlighting the importance of these metrics in assessing treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. Guidetti, A., Dodero, A., Lorenzoni, A., et al.[2023]

In a study of 38 patients treated with CD19 CAR-T cells, significant hematologic toxicities such as neutropenia (94%), thrombocytopenia (80%), and anemia (51%) were observed, often occurring after 21 days post-infusion.

Late hematologic toxicity was more prevalent in patients with high-grade cytokine-release syndrome (CRS) and those recently undergoing stem cell transplantation, suggesting a need for monitoring and management of blood cell levels after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early and late hematologic toxicity following CD19 CAR-T cells. Fried, S., Avigdor, A., Bielorai, B., et al.[2020]

In a phase 1 trial involving 15 pediatric and young adult patients with relapsed or refractory B-ALL, the dual-targeting CAR T-cell therapy AUTO3 demonstrated a favorable safety profile with no severe toxicities reported and an impressive remission rate of 86% one month post-treatment.

Despite the high initial remission rate, the one-year overall survival rate was 60% and event-free survival rate was 32%, indicating that improvements in the persistence of AUTO3 CAR T-cells are necessary to enhance long-term outcomes and prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Cordoba, S., Onuoha, S., Thomas, S., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

CD19-CAR T cell therapy is feasible and safe for treating children and young adults with refractory B-cell malignancies, with a maximum tolerated dose established at 1×10^6 CAR T cells per kg.

The treatment showed potent anti-leukaemic activity, with all toxicities being fully reversible, including severe cases of cytokine release syndrome in 14% of patients, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lee, DW., Kochenderfer, JN., Stetler-Stevenson, M., et al.[2022]

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

In a clinical trial involving 8 patients with advanced B-cell malignancies, 6 achieved remission after receiving T cells genetically modified to target CD19, indicating the efficacy of this CAR T-cell therapy.

While the treatment showed promise in eradicating CD19(+) cells, patients experienced reversible toxicities associated with elevated inflammatory cytokines (IFNγ and TNF), suggesting a need for monitoring and managing these side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Kochenderfer, JN., Dudley, ME., Feldman, SA., et al.[2023]

CD19-targeted CAR T cell therapy has shown remarkable efficacy, achieving complete remission in 70-90% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), highlighting its potential as a powerful treatment for B cell malignancies.

The ongoing phase I study using a non-viral gene transfer method (piggyBac-transposon system) for CD19 CAR T cell therapy in pediatric and young adult patients indicates a promising direction for expanding treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. Nakazawa, Y.[2017]

References

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

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. [2022]

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

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

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

CARs and cancers: questions and answers. [2021]

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

Chimeric antigen receptor T cell therapy for multiple myeloma. [2020]

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

Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. [2023]

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

Early and late hematologic toxicity following CD19 CAR-T cells. [2020]

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

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

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

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. [2022]

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

B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. [2023]

12. Japan pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. [2017]