Cema-cel for B-Cell Lymphoma

(ALPHA3 Trial)

Recruiting at 47 trial locations

Overseen By Allogene Therapeutics, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Allogene Therapeutics

Must not be taking: Anti-CD19 therapies

Disqualifiers: CNS involvement, Autoimmune disease, Infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, open-label study in adult patients who have completed standard first line therapy for large B-cell lymphoma (LBCL) and achieved a complete response or partial response suitable for observation, but who have minimal residual disease (MRD) as detected by the Foresight CLARITY™ Investigational Use Only (IUO) MRD test, powered by PhasED-Seq™. The purpose of the trial is to assess the efficacy and safety of consolidation with cemacabtagene ansegedleucel (cema-cel), an allogeneic CD19 CAR T product, as compared to standard of care observation. The study is conducted in 2 consecutive parts that will be enrolled continuously. In Part A of the study, participants with MRD are randomized to one of two treatment arms or an observation arm. Treatment includes cema-cel following a lymphodepletion regimen of fludarabine and cyclophosphamide administered with or without the anti-CD52 monoclonal antibody, ALLO-647. Part A will culminate with the selection of the lymphodepletion regimen to advance to Part B. Part B will evaluate the selected lymphodepletion regimen followed by cema-cel as compared with observation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves a specific treatment regimen, it's best to discuss your current medications with the trial team to ensure there are no conflicts.

What data supports the effectiveness of the treatment Cemacabtagene Ansegedleucel, ALLO-501.1, ALLO-501A, cema-cel for B-Cell Lymphoma?

While there is no direct data on Cemacabtagene Ansegedleucel, similar CAR T-cell therapies like brexucabtagene autoleucel have shown high response rates in treating mantle cell lymphoma, with 91% of patients responding to the treatment. This suggests that CAR T-cell therapies can be effective for certain types of B-cell lymphomas. ^{1 2 3 4 5}

What makes the treatment Cema-cel unique for B-Cell Lymphoma?

Cema-cel is a type of CAR T-cell therapy, which involves modifying a patient's own immune cells to better recognize and attack cancer cells, making it a personalized treatment option for B-Cell Lymphoma. ^{1 2 3 6 7}

Research Team

Allogene Study Director

Principal Investigator

Allogene Therapeutics, Inc.

Eligibility Criteria

This trial is for adults with large B-cell lymphoma (LBCL) who've had a complete or partial response to first-line therapy but still have minimal residual disease (MRD). They must be suitable for observation and have MRD detected by the Foresight CLARITY™ IUO MRD test.

Inclusion Criteria

I completed my first round of standard cancer treatment without starting another.

My cancer responded well to the first treatment, as shown by PET/CT scans.

I am 18 years old or older.

Exclusion Criteria

I have an active and serious autoimmune disease.

My large B-cell lymphoma has affected my brain or spinal cord, or it has changed from another type of cancer.

I have been treated with anti-CD19 therapies before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants with MRD are randomized to receive cemacabtagene ansegedleucel following a lymphodepletion regimen or observation

8-12 weeks

Multiple visits for treatment and monitoring

Treatment Part B

Evaluation of the selected lymphodepletion regimen followed by cemacabtagene ansegedleucel as compared with observation

8-12 weeks

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Treatment Details

Interventions

• Cemacabtagene Ansegedleucel

Trial Overview The study tests cemacabtagene ansegedleucel (cema-cel), a CD19 CAR T cell therapy, after standard chemo drugs fludarabine and cyclophosphamide, with or without ALLO-647. It compares this treatment's effectiveness and safety against just observing patients.

Participant Groups

Group I: cemacabtagene ansegedleucel, ALLO-647 Experimental Treatment 5 Interventions

Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647.

Group II: cemacabtagene ansegedleucel Experimental Treatment 4 Interventions

Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.

Group III: Observation Experimental Treatment 1 Intervention

Participants do not receive any study treatments. They are observed as per the current standard of care.

Who Is Running the Clinical Trial?

Allogene Therapeutics

Lead Sponsor

Trials

7

Recruited

810+

Headquarters

South San Francisco, USA

Known For

Allogenic CAR T

Top Products

Cemacabtagene ansegedleucel (cema-cel), ALLO-501, ALLO-501A, ALLO-316

Foresight Diagnostics, Inc.

Collaborator

Trials

1

Recruited

250+

Findings from Research

Brexucabtagene autoleucel (brexu-cel) demonstrated high efficacy in treating relapsed/refractory mantle cell lymphoma, with overall and complete response rates of 90% and 82%, respectively, in a real-world setting involving 168 patients.

The safety profile was consistent with earlier trials, showing a 9.1% nonrelapse mortality rate primarily due to infections, and notable rates of cytokine release syndrome (8%) and neurotoxicity (32%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium. Wang, Y., Jain, P., Locke, FL., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma, with a median progression-free survival not reached in the cilta-cel group compared to 11.8 months in the standard-care group, based on a phase 3 trial with 419 participants.

The cilta-cel group also showed higher overall response rates (84.6% vs. 67.3%) and complete response rates (73.1% vs. 21.8%) compared to standard care, although most patients experienced grade 3 or 4 adverse events, including cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. San-Miguel, J., Dhakal, B., Yong, K., et al.[2023]

In the pivotal ZUMA-2 trial, brexucabtagene autoleucel (brexu-cel) showed high efficacy in treating relapsed or refractory mantle cell lymphoma, with an objective response rate of 85% and a complete response rate of 59%, even among high-risk patients.

While brexu-cel has a similar toxicity profile to other CAR T-cell therapies, it is associated with significant treatment-related adverse effects, including severe cytopenias (94%) and neurotoxicity (31%), highlighting the need for careful management by a specialized medical team.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. Anderson, MK., Torosyan, A., Halford, Z.[2022]

In a study of 122 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed aggressive B-cell non-Hodgkin lymphoma, the overall response rate was 70% and the complete response rate was 50%, indicating strong efficacy even in a post-commercial setting with relaxed eligibility criteria.

Patients eligible for the original ZUMA-1 trial had significantly better outcomes, including higher complete response rates (63% vs. 42%) and longer duration of response, progression-free survival, and overall survival, while the rates of severe side effects like cytokine release syndrome and neurotoxicity were consistent with those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Jacobson, CA., Hunter, BD., Redd, R., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) is a CAR-T therapy for adult patients with relapsed or refractory multiple myeloma, and the estimated average healthcare costs for administering this therapy in the US are approximately $160,933 per patient over a 12-month period, excluding the cost of the therapy itself.

The analysis highlights various cost components associated with cilta-cel therapy, including apheresis, bridging therapy, and management of adverse events, which can aid healthcare decision-makers in evaluating the economic implications of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. Jagannath, S., Joseph, N., Crivera, C., et al.[2023]

In the RELIANCE study involving 68 patients with heavily pre-treated relapsed/refractory large B-cell lymphoma, relmacabtagene autoleucel (relma-cel) showed a high objective response rate of 77.59% and a complete response rate of 53.45% after a median follow-up of 17.9 months.

The treatment demonstrated a manageable safety profile, with only 5.1% of patients experiencing severe cytokine release syndrome and 3.4% experiencing severe neurotoxicity, indicating that relma-cel is both effective and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study. Ying, Z., Yang, H., Guo, Y., et al.[2023]

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.

While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. Halford, Z., Anderson, MK., Bennett, LL.[2021]

References

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

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium. [2023]

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

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]

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

Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. [2022]

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

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]

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

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. [2023]

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

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study. [2023]

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

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. [2021]