JCAR017 for Non-Hodgkin's Lymphoma

(TRANSCEND FL Trial)

Recruiting at 127 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

276 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment JCAR017 (Lisocabtagene maraleucel) for Non-Hodgkin's Lymphoma?

Research shows that Lisocabtagene maraleucel, a type of CAR T-cell therapy, has been effective in treating large B-cell lymphoma, a type of Non-Hodgkin's Lymphoma. In a study, 73% of patients responded to the treatment, with 53% achieving complete remission, and 58% of patients survived for at least a year. ^{1 2 3 4 5}

Is lisocabtagene maraleucel (JCAR017) safe for humans?

Lisocabtagene maraleucel (JCAR017) has been shown to have a manageable safety profile in clinical trials for large B-cell lymphoma, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues. Patients need to be closely monitored for at least seven days after receiving the treatment. ^{1 2 4 6 7}

How is the treatment JCAR017 unique for Non-Hodgkin's Lymphoma?

JCAR017, also known as Lisocabtagene maraleucel or Liso-cel, is a unique treatment for Non-Hodgkin's Lymphoma because it is a CAR T-cell therapy that targets CD19 and is manufactured by separately processing CD4 and CD8 T cells, which are then administered in equal doses. This approach aims to balance efficacy and safety, offering a promising option for patients with relapsed or refractory large B-cell lymphomas. ^{1 2 3 6 7}

What is the purpose of this trial?

This is a global Phase 2, open-label, single-arm, multicohort, multicenter study to evaluate efficacy and safety of JCAR017 in adult subjects with r/r FL or MZL. The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. This study is divided into three periods: * Pretreatment, which consists of screening assessments, leukapheresis and the Pretreatment evaluation; * Treatment, which starts with the administration of lymphodepleting (LD) chemotherapy and continues through JCAR017 administration at Day 1 with follow-up through Day 29; * Posttreatment, which includes follow-up assessments for disease status and safety for 5 years.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

References

1. England 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. [2021]

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

Lisocabtagene Maraleucel for the treatment of B-cell lymphoma. [2022]

3. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Lisocabtagene Maraleucel in Relapsed or Refractory Diffuse Large B Cell Lymphoma: What is the Evidence? [2023]

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

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

5. England 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. [2022]

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

Lisocabtagene maraleucel in the treatment of relapsed/refractory large B-cell lymphoma. [2023]

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

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. [2023]