JCAR017 for Non-Hodgkin's Lymphoma

(TRANSCEND FL Trial)

Not currently recruiting at 142 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Disqualifiers: HIV, Hepatitis B/C, Cardiovascular disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called JCAR017 (a type of CAR T-cell therapy) for individuals with certain types of non-Hodgkin's lymphoma, specifically follicular lymphoma (FL) and marginal zone lymphoma (MZL), that have not responded well to previous treatments. The goal is to assess the effectiveness and safety of JCAR017 for these conditions. Participants will first receive chemotherapy to prepare their bodies, followed by an infusion of JCAR017. This trial may suit those recently diagnosed with FL or MZL who have tried other treatments, including anti-CD20 and alkylating agents, but still experience their lymphoma. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the treatment involves chemotherapy and cell therapy, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that JCAR017 is likely to be safe for humans?

Research has shown that JCAR017, also known as lisocabtagene maraleucel or liso-cel, holds promise for safety in treating certain types of non-Hodgkin's lymphoma. Earlier studies revealed that most patients tolerated this treatment well. For instance, many patients with marginal zone lymphoma (MZL) responded positively, indicating the treatment's effectiveness and manageability for many individuals.

Additionally, the FDA has already approved liso-cel for other types of non-Hodgkin's lymphoma, supporting its safety profile. While some side effects may occur, as with any treatment, evidence suggests these are generally manageable. Overall, the findings provide a reassuring picture of its use in treating lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

JCAR017 is unique because it uses a cutting-edge approach called CAR T-cell therapy, which reprograms a patient's own immune cells to specifically target and destroy cancer cells in Non-Hodgkin’s Lymphoma. Unlike conventional treatments such as chemotherapy and radiation, which can affect both healthy and cancerous cells, JCAR017 provides a more targeted attack, minimizing damage to normal cells. This precision in targeting cancer cells is what excites researchers, as it holds the promise of being more effective with potentially fewer side effects compared to existing therapies.

What evidence suggests that JCAR017 might be an effective treatment for Non-Hodgkin's Lymphoma?

Research shows that JCAR017, also known as lisocabtagene maraleucel, holds promise for treating non-Hodgkin's lymphoma, particularly when other treatments have failed. Studies found that 95.5% of patients with relapsed or hard-to-treat marginal zone lymphoma (MZL) responded well to this treatment. This is significant because traditional treatments often result in less than 7% of patients fully responding when chemotherapy fails. In this trial, participants will receive JCAR017 after a preparatory regimen of fludarabine and cyclophosphamide. The treatment involves infusing specially modified immune cells to target and destroy cancer cells. Early evidence suggests these positive responses can be strong and long-lasting, offering new hope for patients with challenging types of lymphoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory indolent B-cell Non-Hodgkin Lymphoma who've had at least one prior therapy including anti-CD20 and an alkylating agent. They should have good organ function, no central nervous system-only cancer, no history of CAR T-cell therapy, and be in fairly good health (ECOG 0 or 1).

Inclusion Criteria

I have been treated with a medication targeting CD20 and one that damages DNA.

I have follicular lymphoma and have been treated with at least one systemic therapy including anti-CD20 and an alkylating agent.

I have suitable veins for a blood filtering procedure.

Exclusion Criteria

I have active hepatitis B or C.

I had a stem cell transplant from a donor within the last 3 months.

I have received CAR T-cell or similar genetic therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pretreatment

Screening assessments, leukapheresis, and Pretreatment evaluation

2-4 weeks

Treatment

Administration of lymphodepleting chemotherapy followed by JCAR017 infusion

4 weeks

Multiple visits for chemotherapy and infusion

Posttreatment

Follow-up assessments for disease status and safety

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• JCAR017

Trial Overview The study tests JCAR017's effectiveness and safety after a lymphodepleting chemotherapy regimen with Cyclophosphamide and Fludarabine. It's a global Phase 2 trial where patients are monitored from treatment through five years post-treatment.

How Is the Trial Designed?

Group I: Administration of JCAR017 Experimental Treatment 3 Interventions

* Subjects will be treated with fludarabine IV (30 mg/m2/day for 3 days) and cyclophosphamide IV (300 mg/m2/day for 3 days) prior to JCAR017 infusion. Refer to the most recent package inserts for further details on administration of these agents. * JCAR017 will be infused on Day 1 at a target dose of 100 × 10\^6 CAR-positive viable T cells (CAR+ T cells), 2 to 7 days after completion of LD chemotherapy. Each JCAR017 dose includes CD4+ CAR+ T cells and CD8+ CAR+ T cells.

JCAR017 is already approved in United States, European Union for the following indications:

Approved in United States as Breyanzi for:

• Relapsed or refractory large B-cell lymphoma

Approved in European Union as Breyanzi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma (FL), or disease not otherwise specified

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

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]

Lisocabtagene Maraleucel (Liso-cel) is a promising CAR-T therapy targeting CD19, showing strong antitumor activity in aggressive B-cell lymphomas with manageable toxicity, as confirmed in the TRANSCEND NHL001 trial.

Preclinical studies indicate that a specific ratio of CD4+ and CD8+ T-cells enhances the effectiveness of Liso-cel, suggesting a well-balanced approach to maximizing both efficacy and safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene Maraleucel for the treatment of B-cell lymphoma. Iragavarapu, C., Hildebrandt, G.[2022]

Lisocabtagene maraleucel (liso-cel) is an effective CAR T cell therapy for relapsed or refractory large B cell lymphoma, showing a 73% objective response rate and a 53% complete remission rate in a study of 344 patients.

The treatment demonstrated a 12-month overall survival rate of 58% for all patients and 86% for those who achieved complete remission, although it was associated with adverse events such as cytokine release syndrome (42%) and neurological issues (30%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene Maraleucel in Relapsed or Refractory Diffuse Large B Cell Lymphoma: What is the Evidence? Kharfan-Dabaja, MA., Yassine, F., Moustafa, MA., et al.[2023]

In a study involving 344 patients with relapsed or refractory large B-cell lymphomas, lisocabtagene maraleucel (liso-cel) demonstrated a high objective response rate of 73%, with 53% achieving a complete response, indicating its efficacy as a treatment option.

The safety profile of liso-cel was acceptable, with a low incidence of severe cytokine release syndrome (2%) and neurological events (10%), suggesting it can be safely administered to patients with various high-risk features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Abramson, JS., Palomba, ML., Gordon, LI., et al.[2021]

Lisocabtagene maraleucel (liso-cel) is an FDA-approved CAR T-cell therapy specifically for treating relapsed/refractory large B-cell lymphoma, with its approval based on the successful TRANSCEND trial.

The review highlights the unique structure and manufacturing process of liso-cel, as well as its efficacy and safety profile demonstrated in landmark trials, including its evaluation in the second-line treatment setting through the TRANSFORM and PILOT studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel in the treatment of relapsed/refractory large B-cell lymphoma. St-Pierre, F., Gordon, LI.[2023]

In a study involving 14 Japanese patients with relapsed or refractory aggressive large B-cell lymphoma, the CAR T-cell therapy lisocabtagene maraleucel (liso-cel) showed a 70% objective response rate and a 50% complete response rate, indicating significant efficacy.

The treatment had a manageable safety profile, with common side effects including neutropenia (90%) and cytokine release syndrome (50%), but no severe (grade ≥3) cytokine release syndrome events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Makita, S., Yamamoto, G., Maruyama, D., et al.[2023]

Lisocabtagene maraleucel (Breyanzi) has been approved by the FDA for treating adults with large B-cell lymphoma who have relapsed or are refractory after initial treatment, highlighting its efficacy in a challenging patient population.

Due to the risk of serious side effects like cytokine release syndrome and neurological toxicities, patients must be closely monitored for at least seven days post-infusion, emphasizing the importance of safety in its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approval for Drug Treating Large B-Cell Lymphoma. Aschenbrenner, DS.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02631044

NCT02631044 | Study Evaluating the Safety and ... We will also determine how long the modified T cells stay in the patient's body and how well JCAR017 works in treating patients with non-Hodgkin's lymphoma ...

2. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Presents-First-Data-from-the-Marginal-Zone-Lymphoma-Cohort-of-the-Transcend-FL-Trial-Demonstrating-Deep-and-Durable-Responses-with-Breyanzi-lisocabtagene-maraleucel/default.aspx

Corporate news details 95.5% of patients with relapsed or refractory marginal zone lymphoma (MZL) treated with lisocabtagene maraleucel (liso-cel) achieved a response.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602637/

Clinical Review - Lisocabtagene Maraleucel (Breyanzi) - NCBI Outcomes are worse in patients with chemotherapy-refractory disease, with only 7% achieving a complete response (CR) to standard treatment and overall survival ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00399

Lisocabtagene Maraleucel Versus Standard of Care for ... Results are reported descriptively. With a median follow-up of 33.9 months, median (95% CI) event-free survival was 29.5 months (9.5 to not ...

5. ashpublications.org ashpublications.org/blood/article/143/5/404/498484/Two-year-follow-up-of-lisocabtagene-maraleucel-in

Two-year follow-up of lisocabtagene maraleucel in relapsed ... Outcomes have been particularly poor for patients with chemotherapy-refractory disease, with CR rates of ∼7% to conventional therapy and an ...

6. breyanzi.com breyanzi.com/

Home | Breyanzi® (lisocabtagene maraleucel) CAR T Cell ... BREYANZI is a prescription medicine used to treat 4 types of non-Hodgkin lymphoma: Large B cell lymphoma, when: your first treatment has not worked or your ...

7. investors.bms.com investors.bms.com/iframes/press-releases/press-release-details/2025/Bristol-Myers-Squibb-Presents-First-Data-from-the-Marginal-Zone-Lymphoma-Cohort-of-the-Transcend-FL-Trial-Demonstrating-Deep-and-Durable-Responses-with-Breyanzi-lisocabtagene-maraleucel/default.aspx

Press Release - Investors - Bristol Myers Squibb 95.5% of patients with relapsed or refractory marginal zone lymphoma (MZL) treated with lisocabtagene maraleucel (liso-cel) achieved a response.

8. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3694/537055/Lisocabtagene-maraleucel-for-R-R-LBCL-in-patients

Lisocabtagene maraleucel for R/R LBCL in patients not ... The safety and efficacy of lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed, 4-1BB CAR T-cell product, is well established ...