CAR T-cell Therapy for Non-Hodgkin Lymphoma

Overseen By Matthew Frigault, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Marcela V. Maus, M.D.,Ph.D.

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Active infection, CNS disease, Heart failure, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using CD79b-19 CAR T cells, a type of immunotherapy, for individuals with Non-Hodgkin Lymphoma that has returned or resisted other treatments. The researchers aim to assess the treatment's effectiveness and understand any side effects. Participants will receive CAR T cells after a process to reduce their white blood cells. Suitable candidates have experienced Non-Hodgkin Lymphoma that hasn't improved after at least two different treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial protocol does not specify if you need to stop your current medications, but ongoing treatment with chronic immunosuppressants or systemic anti-cancer therapy is not allowed. It's best to discuss your specific medications with the trial team.

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

Research shows that CD79b-19 CAR T cells may help fight B-cell lymphomas, a type of cancer. Studies have tested these cells for safety and effectiveness in patients whose Non-Hodgkin Lymphoma has returned or resisted other treatments. Results so far suggest that this treatment is generally well-tolerated. However, as this is early research, more information is needed to fully understand the side effects.

This treatment remains in the early testing stages, meaning researchers are working to find the best dose and monitor for any side effects. Considering joining a trial offers a chance to contribute to this important research while receiving close medical supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD79b-19 CAR T-cell therapy for Non-Hodgkin Lymphoma because it uses a novel approach by genetically modifying a patient's own T cells to better recognize and attack cancer cells. Unlike traditional chemotherapy or targeted therapies, which can affect both healthy and cancerous cells, this treatment specifically targets the CD79b protein on lymphoma cells, potentially leading to more effective and precise cancer cell destruction. Additionally, this treatment is administered in a single dose, offering the promise of quick and potent action against the disease.

What evidence suggests that CD79b-19 CAR T cells might be an effective treatment for Non-Hodgkin Lymphoma?

Research has shown that a new treatment using CD79b-19 CAR T cells may help people with Non-Hodgkin Lymphoma, especially those who haven't had success with other treatments. This therapy modifies a patient's own T cells to find and destroy cancer cells. Studies suggest that targeting CD79b can prevent the cancer from evading the immune system. While early results are promising, more research is needed to determine its effectiveness. This method could provide a new option for patients whose lymphoma has returned or is difficult to treat. ^{1 3 4 5 6}

Who Is on the Research Team?

Matthew Frigault, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain types of Non-Hodgkin Lymphoma that have relapsed or are not responding to treatment. They must have had specific prior therapies, be in a stable condition without severe infections or heart problems, and not be pregnant. Participants should also agree to use contraception.

Inclusion Criteria

Oxygen saturation >92% on room air while awake

Voluntarily sign informed consent form(s)

Subjects must have measurable disease according to appropriate disease specific criteria.

Exclusion Criteria

Significant co-morbid condition or disease which in the judgment of the Principal Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, and/or recent significant traumatic injury.

I have a history of severe heart failure or non-ischemic cardiomyopathy.

I am currently on long-term immune system suppressing drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

White blood cells are collected from participants during Week -3

1 week

1 visit (in-person)

Lymphodepletion

Participants receive 3 days of chemotherapy to decrease the number of lymphocytes

1 week

3 visits (in-person)

Treatment

Participants receive one infusion of CD79b-19 CAR T cells

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• CD79b-19 CAR T cells
• Cyclophosphamide
• Fludarabine

Trial Overview The study tests CD79b-19 CAR T cells in patients with Non-Hodgkin Lymphoma who haven't responded well to other treatments. It includes standard chemotherapy drugs cyclophosphamide and fludarabine used in the lymphodepleting process before administering the CAR T cells.

How Is the Trial Designed?

Group I: CD79b-19 CAR T cells Experimental Treatment 3 Interventions

Prior to receiving CD79b-19 CAR T cells, participants will undergo two preparatory processes: * Leukapheresis: During Week -3 white blood cells will be collected. * Lymphodepletion: On days, -5 to -3 participants will receive 3 days of chemotherapy to decrease the number of lymphocytes CD79b-19 CAR T cells will be administered intravenously on day 0 only. The dose you will receive will depend on the number of participants who have been enrolled prior and how well the dose was tolerated. The CD79b-19 CAR T cells will be administered over approximately 1 hour.

Who Is Running the Clinical Trial?

Marcela V. Maus, M.D.,Ph.D.

Lead Sponsor

Trials

6

Recruited

110+

Published Research Related to This Trial

CAR-T therapy has shown significant success in treating relapsed/refractory B-cell malignancies, utilizing genetically modified T-cells to target and eliminate cancer cells effectively.

Despite its efficacy, CAR-T therapy is associated with serious toxicities such as cytokine release syndrome and neurotoxicity, necessitating improved safety measures, especially as the therapy is being tested in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building safety into CAR-T therapy. Peters, DT., Savoldo, B., Grover, NS.[2023]

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]

CAR-T cell therapy has shown great promise in treating hematological cancers, with two Anti-CD19 CAR-T therapies already approved for CD19-positive leukemia and lymphoma.

However, the therapy can cause serious side effects like cytokine release syndrome and on-target off-tumor toxicity, leading to some patients discontinuing treatment; researchers are exploring various safety strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Yu, S., Yi, M., Qin, S., et al.[2020]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

A patient with primary mediastinal large B-cell lymphoma achieved a complete metabolic response after receiving pembrolizumab following relapse 3.5 months post-CD19-directed CAR T-cell therapy, indicating the potential efficacy of immune checkpoint inhibitors in this setting.

Despite achieving remission, treatment with pembrolizumab was stopped after six cycles due to pneumonitis, highlighting the importance of monitoring for side effects while using immune checkpoint inhibitors after CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review. Dimou, M., Bitsani, A., Bethge, W., et al.[2022]

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.

Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-directed CAR T-cell therapy in B-cell NHL. Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]

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]

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]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

Cellular therapies, including CAR T cells and allogeneic stem cell transplantation, have shown significant effectiveness in treating aggressive non-Hodgkin lymphomas, particularly in patients with poor prognoses.

The article discusses the clinical approach to selecting patients for CD19-directed CAR T cell therapy, emphasizing its growing importance in lymphoma management and the potential of newer cell therapies to enhance immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with cells. Chong, EA., Porter, DL.[2023]

Three CAR-T cell therapies (Yescarta®, Kymriah®, and Breyanzi®) have been approved for treating relapsed or refractory diffuse large B cell lymphomas (DLBCL), significantly improving patient outcomes where conventional treatments fail.

Recent updates and real-life data suggest that CAR-T therapies may be effective earlier in treatment and could be extended to other types of B lymphomas, with new CAR-T cell strategies being explored for Hodgkin's and T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR-T cells in lymphomas: Current and evolving role]. Messéant, O., Houot, R.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06026319

NCT06026319 | CD79b-19 CAR T Cells in Non-Hodgkin ... This is a two-part, non-randomized, open label, single-site Phase 1 study of CD79b-19 CAR T cells as a treatment for relapsed/refractory Non-Hodgkin Lymphoma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6891163/

Chimeric antigen receptor T cells targeting CD79b show ... Conclusions: Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2023-09089

CD79b-19 CAR T Cells for the Treatment of Relapsed or ... This phase I trial tests the safety, side effects, best dose, and effectiveness of CD79b-19 chimeric antigen receptor (CAR) T cells for treating patients ...

4. jitc.bmj.com jitc.bmj.com/content/12/12/e009485

Preclinical development of three novel CARs targeting ... Unfortunately, 60% of patients still relapse after CART19 due to either a loss of expression of the target antigen (CD19) in the tumor cell, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8261235/

A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin ... However, the clinical effect of anti-CD19 CAR-T cells in patients with ALL seems more significant than in patients with lymphoma. In many patients with lymphoma ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10680003/

Chimeric antigen receptor T cells to target CD79b in B- ... Our results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results ...