What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, particularly those involving modified T cells like CAR T-cell therapy, can have several side effects. These include cytokine release syndrome (CRS), which can cause fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Neurological toxicities are also common, leading to confusion, difficulty speaking, seizures, and loss of consciousness. Other side effects may include infections due to immunosuppression, low blood cell counts, and organ toxicities. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several CAR-T cell therapies for the treatment of Non-Hodgkin's Lymphoma. Notably, axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) are approved for certain types of relapsed or refractory large B-cell lymphoma, a subtype of NHL. These therapies involve modifying a patient's T cells to express a chimeric antigen receptor (CAR) that targets CD19, a protein found on the surface of B cells. Brexucabtagene autoleucel (Tecartus) is another CAR-T cell therapy approved for mantle cell lymphoma, a specific type of NHL. These treatments are similar to the JCAR017 trial, which is also investigating the use of modified T cells for antitumor activity in B-cell NHL.

What other types of research exist?

Promising novel alternatives to JCAR017 for Non-Hodgkin's Lymphoma patients include: 1) Anti-CD19-AbTCR, which combines Fab-based antigen recognition with gamma/delta-TCR signaling, showing less cytokine release and comparable tumor inhibition to CTL019 in leukemia models. 2) GMR-targeted CAR T cells, which have demonstrated anti-proliferative effects on leukemic cells in juvenile myelomonocytic leukemia and could be adapted for NHL. These therapies offer innovative approaches with potential benefits in efficacy and safety.

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CAR T-cell Therapy

Modified T Cell Therapy for Non-Hodgkin's Lymphoma

Phase 1

Waitlist Available

Research Sponsored by Juno Therapeutics, a Subsidiary of Celgene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

PET-positive disease by Lugano classification

Relapsed or refractory B-cell NHL, including DLBCL cohort (no longer enrolling): DLBCL, not otherwise specified (NOS; includes transformed DLBCL from indolent histology [tDLBCL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (Swerdlow 2016), primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 lines of systemic therapy or after auto-HSCT.

Must not have

Uncontrolled systemic fungal, bacterial, viral, or other infection

Presence of graft-vs-host disease (GVHD)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests JCAR017, a therapy that modifies a patient's immune cells to fight cancer, in adults with difficult-to-treat non-Hodgkin's lymphoma. The study aims to find the safest and most effective way to use this therapy. JCAR017 has shown potential in treating non-Hodgkin's lymphoma.

Who is the study for?

Adults over 18 with B-cell non-Hodgkin's lymphoma that has returned or didn't respond to treatment can join. They must have had at least two prior treatments, be in good health overall, and not pregnant. People who've had certain recent cancer therapies or infections, other cancers within the last two years (with some exceptions), or active hepatitis or HIV are excluded.

What is being tested?

The trial is testing JCAR017, a modified T cell therapy for lymphoma. Patients will receive either one dose or a two-dose schedule of this treatment to see how safe it is and how well it works against their cancer.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal cells while targeting cancer cells, which could affect different organs. There might also be typical symptoms from infusion like fever and chills.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My PET scan shows active cancer.

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I have a specific type of B-cell lymphoma and my previous treatments, including anthracycline and rituximab, did not work.

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I have MCL that has not improved after at least 2 treatments, including specific drugs.

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I am fully active or can carry out light work.

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I have suitable veins for a blood filtering procedure.

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I have had CD19-targeted therapy and my biopsy confirms CD19-positive lymphoma.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any untreated serious infections.

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I have graft-vs-host disease.

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I have a significant brain-related condition.

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I haven't taken certain strong chemotherapy drugs in the last 2 weeks.

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I have a history of heart disease.

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My cancer has spread into blood vessels or caused clots.

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I have a blood clot that isn't being managed with stable blood thinners.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 15 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting toxicities of JCAR017

Objective response rate (ORR)

Treatment-related adverse events (AEs) as assessed by CTCAE v4.03

Secondary study objectives

Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood

Complete response (CR) rate

Duration of response

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: JCAR017 2-dose schedule (no longer accruing)Experimental Treatment1 Intervention

Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections

Group II: JCAR017 1-dose scheduleExperimental Treatment1 Intervention

Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

JCAR017 (lisocabtagene maraleucel) single-dose schedule

2016

Completed Phase 1

~390

JCAR017 (lisocabtagene maraleucel) 2-dose schedule

2016

Completed Phase 1

~390

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-Hodgkin's Lymphoma (NHL) include chemotherapy, targeted therapy, immunotherapy, and hematopoietic cell transplantation. Chemotherapy works by killing rapidly dividing cells, including cancer cells. Targeted therapies, such as monoclonal antibodies, specifically target cancer cell markers to inhibit their growth. Immunotherapy, including CAR-T cell therapy like JCAR017, involves modifying a patient's T cells to better recognize and attack cancer cells. This is particularly significant for NHL patients as it offers a personalized treatment approach that can lead to more effective and sustained responses, especially in relapsed or refractory cases. Understanding these mechanisms helps patients and doctors make informed decisions about the most appropriate and potentially effective treatment options.