CAR T-cell Therapy for B-Cell Lymphoma

Overseen By Sattva Neelapu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants

Disqualifiers: Active CNS lymphoma, Autoimmune disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of JV-213, a new CAR T-cell therapy, for individuals with B-cell lymphoma that hasn't responded to or has returned after treatment. CAR T-cell therapy uses a person's own immune cells to fight cancer. Those who have tried at least two different treatments for their B-cell lymphoma and still experience symptoms may be suitable for this study. The trial consists of two parts: first, testing different doses of JV-213, and then administering the best dose found to more participants. As a Phase 1 trial, this research focuses on understanding how JV-213 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that at least two weeks or 5 half-lives must have passed since any prior systemic anti-cancer therapy before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that JV-213 is likely to be safe for humans?

Research shows that CAR T-cell therapies, such as JV-213, are usually well-tolerated. These treatments use the body's immune cells to fight cancer. In similar FDA-approved treatments, most patients experience only mild to moderate side effects, such as tiredness, fever, or chills.

Since JV-213 is still under investigation, researchers are collecting precise information about its safety. However, similar treatments in other studies have shown promising safety results, indicating that serious side effects are uncommon. As testing continues, participants in this study will help determine the safest dose levels. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for B-cell lymphoma?

Researchers are excited about JV-213 for B-cell lymphoma because it uses CAR T-cell therapy, a cutting-edge approach that reprograms a patient's own immune cells to target and destroy cancerous B-cells. Unlike traditional chemotherapy and radiation, which can damage healthy cells, CAR T-cell therapy offers a more precise attack on cancer cells, potentially reducing side effects. This innovative treatment also provides hope for patients who have not responded to conventional therapies, offering a new line of defense in the fight against this aggressive form of cancer.

What evidence suggests that JV-213 could be an effective treatment for B-cell lymphoma?

Research has shown that CAR T-cell therapy holds promise for treating aggressive lymphomas unresponsive to standard treatments. In this trial, participants will receive JV-213, a new CAR T-cell therapy targeting a protein called CD79b on B-cell lymphoma cells. Although limited human data exists specifically for JV-213, similar CAR T-cell treatments have successfully managed difficult cases of B-cell lymphomas. These treatments reprogram a patient's immune cells to attack cancer cells. Early signs suggest JV-213 could be effective, but further studies are needed to confirm its benefits. ^{1 2 3 4 5}

Who Is on the Research Team?

Sattva Neelapu, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with B-cell lymphomas that have come back or haven't responded to treatment can join this trial. They must be over 18, have a certain level of overall health and organ function, and at least one measurable lesion. Prior treatments should be completed with recovery from most side effects, except hair loss.

Inclusion Criteria

My heart and lung functions are normal.

I am fully active or can carry out light work.

Patients with measurable lesions per Lugano 2014 Classification

Exclusion Criteria

I have an infection that is not responding to treatment.

I am not willing to use birth control.

I have not received a live vaccine recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JV-213 at escalating doses to determine the maximum tolerated dose

Varies

Multiple visits for dose administration and monitoring

Dose Expansion

Participants receive JV-213 at the recommended dose found in Part 1

Varies

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• JV-213
• Leukapheresis

Trial Overview The trial is testing JV-213 CAR T cell therapy to find the highest dose patients can tolerate without severe side effects. Participants will undergo leukapheresis (a procedure to collect white blood cells) before receiving the therapy.

How Is the Trial Designed?

Group I: Part 2 (dose expansion) Experimental Treatment 2 Interventions

Participants will receive JV-213 at the recommended dose that was found in Part 1.

Group II: Part 1 (dose escalation) Experimental Treatment 2 Interventions

Part 1, the dose of JV-213 participants receive will depend on when you join this study. Up to 3 dose levels of JV-213 will be tested. About 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of JV-213. Each new group will receive a higher dose of JV-213 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of JV-213 is found.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

In a study of 13 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and B cell acute lymphoid leukemia (B-ALL) who previously failed anti-CD19 CAR T cell therapy, anti-CD22 CAR T cell salvage therapy resulted in a higher complete response rate in DLBCL patients, with 4 achieving complete response compared to only 2 in B-ALL.

The anti-CD22 CAR T cell therapy was associated with lower grades of cytokine release syndrome (CRS) compared to the previous anti-CD19 therapy, indicating a potentially safer profile, while overall survival for DLBCL patients was approximately 6.1 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy. Zhu, H., Deng, H., Mu, J., et al.[2022]

In a study of 129 adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) treated with CD19-directed CAR T therapy, 95.4% were hospitalized during treatment, with a median hospital stay of 17 days, highlighting the intensive care required during this therapy.

The estimated 6-month risk of requiring subsequent treatment after CAR T was 36.2%, indicating a significant chance of treatment failure, and emphasizing the need for effective salvage therapies for DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. Jalbert, JJ., Wu, N., Chen, CI., et al.[2022]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

CAR-T cell therapy shows promising efficacy in treating relapsed/refractory B-cell lymphoma, particularly in older patients and those with specific pathological types, achieving high response and complete remission rates across 17 studies.

While the treatment is generally safe, with most side effects like cytokine-releasing syndrome (CRS) and neurotoxicity being reversible, careful monitoring of these toxicities is essential during clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor-T cells in the treatment of B cell lymphoma: a systematic review and meta-analysis. Zheng, XH., Zhang, XY., Dong, QQ., et al.[2023]

CAR.λ T cells effectively target and kill Igλ+ lymphoma cells and chronic lymphocytic leukemia (CLL) cells, showing similar antitumor activity to the established CAR.CD19 T cells in both laboratory and animal models.

Importantly, CAR.λ and CAR.κ T cells selectively deplete only the corresponding light chain-expressing normal B cells, preserving the other type, which suggests a safer approach with minimal impact on the immune system's ability to produce antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. Ranganathan, R., Shou, P., Ahn, S., et al.[2022]

Autologous cellular immunotherapy, including immune checkpoint blockade and CAR T-cells, shows promise for treating B-cell non-Hodgkin lymphomas (B-NHL), but its effectiveness is often limited compared to other cancers, possibly due to T-cell dysfunction and regulatory T-cell expansion.

The review highlights the need to understand the biological mechanisms behind the varying responses to these therapies in different types of B-NHL, such as diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and suggests strategies to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the Hurdles of Autologous T-Cell-Based Therapies in B-Cell Non-Hodgkin Lymphoma. van Bruggen, JAC., Martens, AWJ., Tonino, SH., et al.[2021]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

In a study involving 11 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the combination of CD19 CAR-T cells and the anti-PD-1 antibody nivolumab was found to be safe, with no dose-limiting toxicities and manageable side effects like cytokine release syndrome in a minority of patients.

The treatment showed promising efficacy, achieving an objective response rate of 81.81% and a complete response rate of 45.45%, indicating strong anti-lymphoma activity that warrants further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. Cao, Y., Lu, W., Sun, R., et al.[2020]

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

A new T-cell receptor (TCR)-based immunotherapy targeting the CD79b protein shows promise against B-cell malignancies, demonstrating strong reactivity to cancerous B cells while sparing non-cancerous cells.

The study highlights the importance of considering aberrant gene expression in non-cancerous cells when selecting targets for TCR-based therapies, as some normal cells may express low levels of the target antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic targeting of the BCR-associated protein CD79b in a TCR-based approach is hampered by aberrant expression of CD79b. Jahn, L., Hombrink, P., Hassan, C., et al.[2021]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

A novel CAR T-cell therapy targeting CD79b has been developed, showing strong antitumor activity against B-cell lymphomas in both laboratory and animal models, including the ability to attack tumors that have relapsed after CD19-targeted therapies.

The CD79b CAR T cells demonstrated effective proliferation and cytotoxic activity without significant signs of exhaustion, supporting their potential for use in a phase 1 clinical trial for patients with relapsed or refractory B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas. Chu, F., Cao, J., Liu, J., et al.[2023]

CAR T-cell therapy has shown remarkable success in treating B-cell acute lymphoblastic leukemia by targeting the CD19 marker, which is present on most B-cell tumors.

The therapy is being explored for other B-cell malignancies, including chronic lymphocytic leukemia and various types of lymphoma, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Pegram, HJ., Smith, EL., Rafiq, S., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05773040

NCT05773040 | A Phase 1 Study of JV-213 Autologous ... A Phase 1 Study of JV-213 Autologous CD79b-targeting Chimeric Antigen Receptor T-cell Therapy in Adults With Relapsed or Refractory B-cell Lymphomas.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02055

JV-213 Autologous CD79b-Targeting CAR-T Cell Therapy ... This phase I clinical trial tests the safety, side effects, and best dose of anti-CD79b chimeric antigen receptor (CAR) T cells (JV-213) to treat adults with B ...

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0938.html

A phase 1 study of JV-213 autologous CD79b-targeting ... A phase 1 study of JV-213 autologous CD79b-targeting chimeric antigen receptor T-cell therapy in adults with relapsed or refractory B-cell lymphomas.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10727106/

Management of aggressive lymphoma after CAR T-cell ... CAR T-cell therapy has transformed the management of chemorefractory DLBCL based on the pivotal, single-arm phase 2 trials leading to approval ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05773040/a-phase-1-study-of-jv-213-autologous-cd79b-targeting-chimeric-antigen-receptor-t-cell-therapy-in-adults-with-relapsed-or-refractory-b-cell-lymphomas?mp=BCF&study_type=Observational&page=3&id=424&slug=solid-tumors

A Phase 1 Study of JV-213 Autologous CD79b-targeting ... To find the highest tolerable dose of JV-213 (a type of autologous CAR T cell therapy) that can be given to patients who have B-cell lymphoma