What side effects are associated with this type of intervention?

Chimeric Antigen Receptor (CAR) T-cell therapy, such as the one being studied in the JCAR017 trial, is associated with several significant side effects. The most common and serious side effects include cytokine release syndrome (CRS), which can cause high fever, low blood pressure, and difficulty breathing, and neurotoxicity, which can lead to confusion, seizures, and encephalopathy. Other side effects include cytopenias (low blood cell counts), infections, and fatigue. These side effects can be severe and require close monitoring and management.

What prior FDA approvals exist?

Brexucabtagene autoleucel (formerly KTE-X19) is a Chimeric Antigen Receptor (CAR)-T cell therapy that has been approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma. This therapy targets CD19 and has shown high overall response rates and complete remission in a significant number of patients. The approval of brexucabtagene autoleucel highlights the potential of CAR-T cell therapies in treating lymphomas, similar to the investigational JCAR017 therapy being studied for relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

What other types of research exist?

Promising novel alternatives to JCAR017 for lymphoma patients include the bicistronic CD19.28ζ/CD22.BBζ CAR T-cell construct, which has shown enhanced cytokine production and efficacy in heavily pretreated B-cell acute lymphoblastic leukemia (B-ALL) patients. Additionally, immune checkpoint inhibitors such as pembrolizumab and nivolumab, either alone or in combination with other agents like axitinib, have demonstrated clinical activity in various types of advanced lymphomas. These therapies represent significant advancements and offer new options for lymphoma patients considering treatment in 2024.

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CAR T-cell Therapy

JCAR017 for Chronic Leukemia or Lymphoma

Q: What is the mechanism of action of this treatment?

Chimeric Antigen Receptor (CAR) T-cell therapy is a cutting-edge treatment for lymphoma that involves modifying a patient's own T-cells to express receptors specific to cancer cells. These engineered T-cells are then infused back into the patient, where they can recognize and attack lymphoma cells. This therapy is significant for lymphoma patients because it offers a targeted approach that can lead to durable remissions, especially in cases where the disease is refractory or has relapsed after conventional treatments. The ability of CAR T-cells to specifically target and destroy cancer cells while sparing normal cells represents a major advancement in lymphoma treatment.

Phase 1 & 2

Recruiting

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

Confirmation of CD19-positive disease if prior CD19-targeted therapy has been administered

Diagnosis of SLL with lymphadenopathy and/or splenomegaly and < 5×10^9 CD19+ CD5+ clonal B lymphocytes/L [< 5000/µL] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL

Must not have

Subjects with Richter's transformation

Presence of acute or extensive chronic graft versus host disease (GVHD)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 48 months post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests JCAR017, a therapy using modified immune cells, in adults with hard-to-treat CLL or SLL. It aims to see if these enhanced immune cells can better fight the cancer.

Who is the study for?

Adults with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) who have failed multiple prior therapies can join. Participants must have adequate organ and bone marrow function, not be pregnant, and cannot have active infections like hepatitis B/C or HIV.

What is being tested?

The trial is testing JCAR017 alone or in combination with either ibrutinib or venetoclax to treat CLL/SLL. It's a multi-phase study starting with finding the right dose of JCAR017 before moving on to test its effectiveness and safety at that dose.

What are the potential side effects?

Potential side effects include reactions related to gene therapy, infection risks due to weakened immune system, liver problems, kidney issues, breathing difficulties, heart complications from chemotherapy drugs used alongside JCAR017.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is CD19 positive, even after CD19-targeted treatment.

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I have SLL with specific symptoms and a certain level of B lymphocytes.

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I have tried and not responded to BTK inhibitor treatment or was deemed ineligible for it.

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I am fully active and can carry on all my pre-disease activities without restriction.

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I am suitable for or already have a central or peripheral line for blood filtering procedures.

Exclusion Criteria

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

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My condition has progressed to Richter's transformation.

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I am experiencing severe symptoms from a transplant rejection.

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I have a significant brain or nervous system condition.

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My cancer has spread into blood vessels.

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I have unmanaged blood clots in my veins.

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I am not taking any strong medication that affects liver enzymes with my current cancer treatment.

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I have had another type of cancer in the last 2 years.

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My cancer has spread to my brain or spinal cord.

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I have received gene therapy before.

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I do not have active hepatitis B, C, or HIV.

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I do not have any untreated infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 48 months post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 48 months post treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 48 months post treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: adverse events

Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: laboratory abnormalities

Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm

+7 more

Secondary study objectives

Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Duration of complete response (DoCR)

Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Duration of response (DOR)

Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: MRD negative response rate in peripheral blood

+44 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: Phase 2 JCAR017 monotherapyExperimental Treatment1 Intervention

Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm

Group II: Phase 2 JCAR017 Double-Exposed Monotherapy Expansion (DEME)Experimental Treatment1 Intervention

Subjects will receive JCAR017 monotherapy

Group III: Phase 1 JCAR017 monotherapyExperimental Treatment1 Intervention

Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)

Group IV: Phase 1 JCAR017 + venetoclaxExperimental Treatment2 Interventions

Subjects will receive venetoclax as bridging anticancer therapy until lymphodepletion chemotherapy/ JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm. After JCAR017 infusion subjects will receive venetoclax until Day 90.

Group V: Phase 1 JCAR017 + ibrutinibExperimental Treatment1 Intervention

Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm + ibrutinib

0 / 16Eligibility 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

Chimeric Antigen Receptor (CAR) T-cell therapy is a cutting-edge treatment for lymphoma that involves modifying a patient's own T-cells to express receptors specific to cancer cells. These engineered T-cells are then infused back into the patient, where they can recognize and attack lymphoma cells. This therapy is significant for lymphoma patients because it offers a targeted approach that can lead to durable remissions, especially in cases where the disease is refractory or has relapsed after conventional treatments. The ability of CAR T-cells to specifically target and destroy cancer cells while sparing normal cells represents a major advancement in lymphoma treatment.