Cema-cel for B-Cell Lymphoma

(ALPHA3 Trial)

Recruiting at 56 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called cemacabtagene ansegedleucel (cema-cel) for people with B-cell lymphoma who have residual disease after their first treatment round. The researchers aim to determine if cema-cel is more effective than the current standard practice of simply observing patients. Participants will either receive the new treatment or be observed without additional treatment. This trial suits adults who have completed initial therapy for large B-cell lymphoma and still have minimal residual disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research shows that cemacabtagene ansegedleucel, or cema-cel, has a manageable safety profile in patients with large B-cell lymphoma. In earlier studies, patients who received this CAR T-cell therapy (a treatment using the body's own immune cells) experienced encouraging results. Side effects occurred but were not too severe, and medical teams managed them effectively.

Notably, these results appeared mostly in patients who hadn't undergone similar treatments before. While researchers continue to study the safety of cema-cel, current evidence suggests it is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell lymphoma, which often involve chemotherapy and monoclonal antibodies, cemacabtagene ansegedleucel is a type of CAR T-cell therapy. This treatment is unique because it genetically modifies a patient's own T-cells to better recognize and attack cancer cells. Researchers are excited about this approach because it offers a more personalized and potentially more effective way to target lymphoma, with the promise of longer-lasting remissions and fewer side effects compared to traditional therapies.

What evidence suggests that cemacabtagene ansegedleucel could be an effective treatment for B-cell lymphoma?

Research shows that cemacabtagene ansegedleucel, or cema-cel, holds promise for treating large B-cell lymphoma (LBCL). Studies found that this treatment achieved an overall response rate (ORR) of 58%, indicating that 58% of patients experienced tumor reduction or disappearance. Many patients achieved a complete response (CR), with no detectable signs of cancer. In this trial, participants will receive cema-cel after a lymphodepletion regimen. Cema-cel uses specially modified immune cells to target and attack cancer cells. It has provided lasting results while keeping side effects manageable for patients. This suggests that cema-cel could be an effective option for those with this type of lymphoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Allogene Study Director

Principal Investigator

Allogene Therapeutics, Inc.

Are You a Good Fit for This Trial?

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: cemacabtagene ansegedleucel Experimental Treatment 4 Interventions

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

Group II: 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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39946666/

Allogeneic Chimeric Antigen Receptor T-Cell ... - PubMed - NIH Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01933

Allogeneic Chimeric Antigen Receptor T-Cell Products ... Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve patients with R/R LBCL.

3. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-announces-publication-durable-response

Allogene Therapeutics Announces Publication of Durable ... Cemacabtagene ansegedleucel, or cema-cel, is a next generation anti-CD19 AlloCAR T™ investigational product for the treatment of large B cell ...

4. bloodcancerstoday.com bloodcancerstoday.com/post/alpha2-alpha-trials-cema-cel-shows-promising-results-in-lbcl

Cema-Cel Shows Promising Results in LBCL Cema-cel is a feasible treatment option and can induce durable responses in patients with LBCL, achieving an ORR of 58% and a CR rate of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06500273

Study Details | NCT06500273 | Consolidation of First-Line ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04416984

NCT04416984 | Safety and Efficacy of ALLO-501A Anti- ... The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024017749

A Phase 1b Study Evaluating the CD19 Allogeneic CAR T ... The phase 1 ALPHA2 (NCT04416984) study of cema-cel in patients with R/R large B-cell lymphoma demonstrated promising efficacy and a manageable safety profile.