CRG-022 for Large B-Cell Lymphoma

(FIRCE-1 Trial)

No longer recruiting at 32 trial locations

Overseen By CargoTx Email address

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CARGO Therapeutics

Disqualifiers: Infections, Allogeneic transplant, 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

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called firi-cel (also known as CRG-022) for individuals with large B-cell lymphoma, a type of blood cancer that has returned or not responded to other treatments. The trial aims to assess the safety and effectiveness of firi-cel when administered after chemotherapy. Participants are divided into three groups, each receiving the treatment slightly differently based on their previous therapies. Suitable candidates for this trial include those whose large B-cell lymphoma has relapsed or is refractory after prior treatments and who have at least one visible tumor. Participants must be willing to remain near the treatment center for follow-up. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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 CRG-022 is likely to be safe for humans?

Research shows that firicabtagene autoleucel (firi-cel), a type of CAR T-cell therapy targeting CD22, may help treat large B-cell lymphoma (LBCL). Studies suggest this treatment can lead to lasting remissions and even long-term survival for some patients. However, safety information is also important to consider.

In earlier studies, some patients experienced side effects, which is common with CAR T-cell therapies. These side effects can include cytokine release syndrome (a reaction that can cause fever and low blood pressure) and nerve damage. Not everyone will have these side effects, and medical teams closely monitor patients to manage any issues.

The current phase of the study indicates some understanding of the treatment's safety in humans. This phase usually means the treatment has shown acceptable safety in earlier trials. Those considering joining this trial will receive close monitoring and support from their healthcare team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CRG-022 because it offers a novel approach to treating Large B-Cell Lymphoma. Unlike standard treatments like chemotherapy, immunotherapy, or CAR T-cell therapy, CRG-022 involves a single infusion of firi-cel following conditioning chemotherapy. This unique mechanism targets cancer cells more directly, potentially improving outcomes for patients who have relapsed or have refractory forms of the disease. Additionally, one of the trial's exciting aspects is the use of a "non-conforming" product in one cohort, which researchers believe is safe and could provide valuable insights into treatment flexibility and effectiveness.

What evidence suggests that CRG-022 might be an effective treatment for large B-cell lymphoma?

Research has shown that firicabtagene autoleucel (firi-cel) may effectively treat large B-cell lymphoma (LBCL), particularly in patients whose condition has worsened after other treatments. In this trial, participants will receive a single infusion of firi-cel following conditioning chemotherapy. Studies have found that this therapy, which uses specially modified immune cells called T-cells, can keep cancer under control for extended periods. These T-cells are designed to find and attack cancer cells. Early results suggest that firi-cel might help patients with relapsed or hard-to-treat LBCL live longer. However, some trials with firi-cel have been stopped, indicating mixed results in different situations. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Large B-cell Lymphoma that's come back or hasn't responded to treatment. They must have a certain level of neutrophils, a type of white blood cell, and be well enough for daily activities (ECOG status 0-1). Some need to have tried specific previous therapies like CD19-directed CAR T-cell therapy or bispecific T-cell engaging antibodies.

Inclusion Criteria

My blood, kidney, and liver tests are within normal ranges.

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

My large B-cell lymphoma has returned or is not responding to treatment.

Exclusion Criteria

I am currently on antibiotics for an infection.

I have had a stem cell transplant from a donor.

Clinically significant concurrent medical illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy prior to the infusion of firi-cel

1-2 weeks

Treatment

Participants receive a single infusion of firi-cel

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Long-term Follow-up

Participants are monitored for long-term safety and survival outcomes

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CRG-022

Trial Overview The study tests CRG-022, an experimental CAR T-cell therapy targeting CD22 in the body. It's given alongside Fludarabine and Cyclophosphamide Monohydrate as conditional treatments. The goal is to see how safe it is, how the body reacts to it, and if it works against relapsed/refractory large B-cell lymphoma.

How Is the Trial Designed?

Group I: Experimental Drug (Cohort 3) Experimental Treatment 3 Interventions

Patients with relapsed or refractory Large B-cell lymphoma who have previously been treated with bispecific T-cell engaging antibody therapy will receive a single infusion of firi-cel following conditioning chemotherapy.

Group II: Experimental Drug (Cohort 2: non-conforming product) Experimental Treatment 3 Interventions

Single infusion of firi-cel following conditioning chemotherapy (patients in this cohort will receive non-conforming firi-cel that is deemed safe to administer).

Group III: Experimental Drug (Cohort 1) Experimental Treatment 3 Interventions

Single infusion of firi-cel following conditioning chemotherapy

Who Is Running the Clinical Trial?

CARGO Therapeutics

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

In the ZUMA-12 study involving 40 patients with high-risk large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high complete response rate of 78% and an overall response rate of 89%, indicating its effectiveness as a first-line treatment.

The safety profile of axi-cel was manageable, with only 8% of patients experiencing severe cytokine release syndrome and 23% experiencing neurological events, and no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Neelapu, SS., Dickinson, M., Munoz, J., et al.[2023]

Axicabtagene ciloleucel and brexucabtagene autoleucel are effective anti-CD19 T-cell therapies that have shown high response rates in patients with relapsed and refractory B-cell malignancies, leading to FDA approvals for specific types of lymphoma.

Despite their effectiveness, these therapies can cause significant toxicities, such as cytokine release syndrome and neurologic issues, which necessitate careful management and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. Reagan, PM., Friedberg, JW.[2021]

In a study of 352 adult patients with aggressive large B-cell lymphoma treated with CAR T-cell therapy, 74.4% developed cytokine release syndrome (CRS), but this did not significantly affect their progression-free or overall survival rates compared to those who did not develop CRS.

High peak ferritin levels (>5000 ng/mL) and elevated lactate dehydrogenase levels before treatment were associated with worse survival outcomes, indicating that these factors may be more critical for predicting patient prognosis than the occurrence of CRS itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome. Bhaskar, ST., Patel, VG., Porter, DL., 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]

The ZUMA-5 trial demonstrated that axicabtagene ciloleucel (axi-cel) provides durable responses in patients with relapsed/refractory follicular lymphoma, showing significant improvements in overall survival and progression-free survival compared to the SCHOLAR-5 control cohort.

With a median follow-up of 29.4 months for ZUMA-5 and 25.4 months for SCHOLAR-5, the analysis confirmed that axi-cel's efficacy remains strong over time, with hazard ratios indicating a 48% reduction in the risk of death and a 72% reduction in the risk of disease progression compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Palomba, ML., Ghione, P., Patel, AR., et al.[2023]

In a phase 2 trial involving 61 patients with relapsed or refractory large B-cell lymphoma, lisocabtagene maraleucel demonstrated a high overall response rate of 80%, indicating its efficacy as a second-line treatment for patients not intended for stem-cell transplantation.

The treatment was generally safe, with no treatment-related deaths reported; however, common serious side effects included neutropenia and cytokine release syndrome, which occurred in 38% of patients, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Sehgal, A., Hoda, D., Riedell, PA., et al.[2022]

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]

Brexucabtagene autoleucel (KTE-X19) CAR T-cell therapy showed a remarkable 91% objective response rate and 68% complete response rate in 68 patients with relapsed/refractory mantle cell lymphoma after a median follow-up of 35.6 months, indicating its efficacy in this challenging patient population.

The therapy demonstrated durable long-term responses with manageable safety, as late-onset toxicities were infrequent, occurring in only 3% of patients, suggesting that KTE-X19 is a safe and effective treatment option even for those with high-risk characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Wang, M., Munoz, J., Goy, A., et al.[2023]

In a study of 258 patients receiving CAR T-cell therapy for large B-cell lymphoma, 72% experienced severe neutropenia, with a median duration of 9 days, highlighting the significant risk of hematotoxicity associated with this treatment.

The CAR-HEMATOTOX model was developed to predict the duration of severe neutropenia based on baseline markers like platelet count and inflammation, showing high accuracy (AUC 0.89) and helping to identify patients at greater risk for prolonged cytopenia, which can guide management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Rejeski, K., Perez, A., Sesques, P., et al.[2022]

In a phase 2 trial involving 111 patients with refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 82%, with 54% achieving a complete response, indicating its efficacy as a treatment option.

The treatment was associated with significant adverse events, including neutropenia in 78% of patients and neurologic events in 28%, highlighting the need for careful monitoring of safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. Neelapu, SS., Locke, FL., Bartlett, NL., et al.[2023]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05972720

NCT05972720 | A Phase 2 Study of Firi-cel in Patients With ... This Phase 2 study is designed to evaluate the safety and the efficacy of firi-cel in patients with R/R LBCL that has progressed after CD19-directed CAR T-cell ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/69/530621/CD22-Directed-CAR-T-Cell-Therapy-for-Large-B-Cell

CD22-Directed CAR T-Cell Therapy for Large B-Cell ... CAR22 provides durable remissions and long-term survival in CAR19-progressing LBCL patients. Late progression or lymphoma-specific death was ...

3. onclive.com onclive.com/view/cargo-therapeutics-to-discontinue-phase-2-study-of-firi-cel-in-r-r-lbcl

CARGO Therapeutics to Discontinue Phase 2 Study of Firi- ... CARGO Therapeutics announced that it will discontinue the phase 2 FIRCE-1 trial evaluating firi-cel in relapsed/refractory large B-cell lymphoma.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT05972720

A Phase 2 Study of Firi-cel in Patients With Relapsed/ ... 71 patients have been dosed in the potentially pivotal Phase 2 study of firi-cel, FIRCE-1; CARGO continues to achieve strong manufacturing success of firi-cel.

5. trialx.com trialx.com/clinical-trials/listings/235085/a-phase-2-study-of-firi-cel-in-patients-with-relapsedrefractory-large-b-cell-lymphoma/

A Phase 2 Study of Firi-cel in Patients With Relapsed/ ... Firicabtagene autoleucel (firi-cel) is an autologous CAR T-cell therapy targeting CD22, a common B-cell antigen widely expressed in LBCL. This ...

6. bloodcancerstoday.com bloodcancerstoday.com/post/firicabtagene-autoleucel-potentially-curative-for-car19-progressing-lbcl

CAR22 Shows Lasting Response in LBCL Subgroup Patients with CAR-19 progressing large B-cell lymphoma had durable remissions and long-term survival on treatment with firicabtagene ...