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

Not currently recruiting at 4 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Synthekine

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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days post infusion

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment involving CAR-T cell therapy combined with IL-2 for certain blood cancers. The main goal is to determine if the combination of SYNCAR-001 (Autologous CD19 CAR-T Cell Therapy) and STK-009 (Orthogonal IL-2) works safely and effectively in cancers with the CD19 marker. Individuals who have tried other treatments but still have certain blood cancers, such as Chronic Lymphocytic Leukemia (CLL) or some Non-Hodgkin's Lymphomas (NHL), might be suitable candidates. Eligibility requires that these specific blood cancers do not affect the brain or spinal cord. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of SYNCAR-001 and STK-009 is promising in terms of safety. Early studies found that patients with recurring or hard-to-treat blood cancers generally tolerated this treatment well. Reports indicate a good safety profile, meaning patients did not experience severe side effects. This is encouraging for potential trial participants, as it suggests the treatment might be safe. However, since this is the first time researchers are testing this treatment in humans, they are closely monitoring for any possible risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SYNCAR-001 for blood cancer because it combines CAR-T cell therapy with the cytokine IL-2, administered as STK-009. Unlike traditional treatments like chemotherapy and radiation, which can be harsh on the body, SYNCAR-001 harnesses the power of the patient's own immune cells to target cancer. This approach aims to enhance the immune response specifically against cancer cells, potentially leading to more effective and less toxic treatment outcomes. Additionally, the combination with IL-2 may further boost the effectiveness of the CAR-T cells, offering hope for improved remission rates.

What evidence suggests that this trial's treatments could be effective for blood cancer?

In this trial, participants will receive a combination of SYNCAR-001 and STK-009, which research has shown may help treat certain blood cancers. Early results suggest this treatment is safe and effective. Patients with recurrent or hard-to-treat blood cancers have responded positively. The treatment enhances the growth and function of special CAR-T cells, using unique technology to boost CAR-T cell therapy. While more research is needed, early studies are promising and suggest potential benefits for people with these blood cancers. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• STK-009
• SYNCAR-001

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.

How Is the Trial Designed?

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

SYNCAR-001 is already approved in United States for the following indications:

Approved in United States as SYNCAR-001 for:

• Severe, refractory systemic lupus erythematosus (SLE) without lymphodepletion

Who Is Running the Clinical Trial?

Synthekine

Lead Sponsor

Trials

3

Recruited

290+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05665062

NCT05665062 | Autologous CD19 CAR-T Cell Therapy ... This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies. ... IL-2 cytokine selective for SYNCAR-001 CAR-T ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3453/529717/A-Phase-1-Study-to-Evaluate-the-Safety-and

A Phase 1 Study to Evaluate the Safety and Tolerability of a ... We report initial data investigating the combination of SYNCAR-001 + STK-009 (STK-009-101) in adults with relapsed or refractory (r/r) mature CD19+ hematologic ...

3. synthekine.com synthekine.com/news/synthekine-presents-positive-initial-results-from-phase-1-clinical-trial-of-cd19-car-t-syncar-001-and-orthogonal-il-2-stk-009-combination-therapy-for-treatment-of-hematologic-malignancies-at-ash-2/

Synthekine Presents Positive Initial Results from Phase 1 ... SYNCAR-001 + STK-009 is a cytokine-enabled cell therapy regimen based on Synthekine's proprietary orthogonal IL-2 technology.

4. bloodcancerstoday.com bloodcancerstoday.com/post/early-results-highlight-promise-of-autologous-car-t-cell-combination-therapy

Early Results Highlight Promise of Autologous CAR T-Cell ... The combination of SYNCAR-001and STK-009 exhibited favorable safety, efficacy, and chimeric antigen receptor (CAR) T-cell metrics in patients with relapsed or ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124062050

A Phase 1 Study to Evaluate the Safety and Tolerability of ... STK-009 administered with only 30×10 6 SYNCAR-001 CAR T cells has a favorable safety profile, durable efficacy, and meaningful SYNCAR-001 fitness, expansion ...