CNTY-101 for B-Cell Malignancies

(ELiPSE-1 Trial)

Recruiting at 15 trial locations

Overseen By Nikolaus Trede

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Century Therapeutics, Inc.

Disqualifiers: CNS-only malignancy, CNS pathology, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called CNTY-101 to see if it is safe and effective for patients whose B-cell cancers have come back or did not respond to previous treatments. The treatment works by targeting a marker called CD19 on the cancer cells.

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

The trial protocol mentions a 'washout period' (time without taking certain medications), but it does not specify which medications are prohibited. It's best to discuss your current medications with the trial team to see if any need to be stopped.

What safety data exists for CNTY-101 in B-Cell Malignancies?

The Sleeping Beauty CD19 CAR T-cell therapy, similar to CNTY-101, showed an excellent safety profile in a phase 1 trial with no serious adverse events directly linked to the treatment. Mild cytokine release syndrome (a reaction where the immune system releases too many proteins into the blood too quickly) was observed in some patients, but no neurotoxicity (nerve damage) or dose-limiting toxicities were reported. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for people with CD19-positive B-cell Non-Hodgkin's Lymphoma that has come back or hasn't responded to treatment. They must have tried at least two or three prior therapies, including a CD20-targeted agent and an anthracycline or alkylator. Participants should be fairly active (ECOG 0-1), have measurable disease, good organ function, and a life expectancy of over 12 weeks.

Inclusion Criteria

Measurable disease on screening evaluations

My lymphoma is CD19-positive and has come back or didn't respond to treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Any condition that confounds the ability to interpret data from the study

I have a significant brain or spinal cord condition.

Use of prohibited medications within the washout period defined in the protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CNTY-101 administration

1 week

Treatment

Participants receive CNTY-101, either as a single dose or three doses over three weeks, with or without supplemental IL-2

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• CNTY-101

Trial Overview The ELiPSE-1 study is testing CNTY-101 in patients with certain types of blood cancer. It's the first phase where they're figuring out safe doses, how the body processes the drug, and if it works well against these cancers. Patients will also receive lymphodepleting chemotherapy and IL-2 as part of their treatment.

Participant Groups

Group I: Dose Escalation: Schedule B Experimental Treatment 3 Interventions

LDC will be followed by administration of CNTY-101, 3 times over 3 weeks, alone or with supplemental IL-2.

Group II: Dose Escalation: Schedule A Experimental Treatment 3 Interventions

Lymphodepleting chemotherapy (LDC) will be followed by single dose administration of CNTY-101, alone or with supplemental human recombinant interleukin 2 (IL-2).

Who Is Running the Clinical Trial?

Century Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

500+

Findings from Research

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]

Anti-CD19 CAR-modified T cells have demonstrated a 48% overall response rate in treating B-cell malignancies, with complete responses observed in 24% of patients across six phase I clinical trials involving 50 patients.

The study found that conditioning chemotherapy significantly improves progression-free survival (PFS), making it a crucial factor for enhancing the efficacy of CAR T-cell therapy, while the treatment was generally well tolerated with temporary adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Zhu, Y., Tan, Y., Ou, R., et al.[2022]

In a study of 20 newly diagnosed patients with Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL), Zytux™ showed an overall response rate of 85%, with 35% achieving a complete response and 50% a partial response, indicating its efficacy in treating these conditions.

Zytux™ demonstrated a safety profile comparable to the reference drug MabThera®, suggesting it may be a viable alternative with similar or improved safety and efficacy for patients with NHL and CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biosimilar rituximab (ZytuxTM) in newly diagnosed patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. Alwan, AF., Abdulsahib, MA., Abbas, DD., et al.[2020]

In a phase I study involving 10 patients with refractory diffuse large B-cell lymphoma (DLBCL), the anti-CD19 CAR T cell therapy (C-CAR011) demonstrated a 50% overall response rate at 12 weeks, indicating promising efficacy for this treatment.

The therapy showed a favorable safety profile, with 90% of patients experiencing cytokine release syndrome but no severe (grade ⩾ 3) cases or neurotoxicity, suggesting it is a safe option for patients with heavily treated DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. Fan, L., Wang, L., Cao, L., et al.[2022]

Dual-targeting CAR-T cell therapy shows promising efficacy in treating B cell malignancies, with a 77% overall response rate and 52% complete response rate in patients with B cell non-Hodgkin lymphoma (B-NHL), and a 92% complete response rate in patients with B cell acute lymphoblastic leukemia (B-ALL).

The therapy has a manageable safety profile, with grade ≥3 cytokine release syndrome occurring in 14% of B-NHL patients and 11% of B-ALL patients, indicating that while there are risks, the benefits may outweigh them for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis. Yu, M., Zhang, Q., Kong, F., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biosimilar rituximab (ZytuxTM) in newly diagnosed patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. [2020]

4. China pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. [2022]

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

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis. [2023]