CAR-T + Nivolumab for Hodgkin Lymphoma

(ACTION Trial)

Not currently recruiting at 4 trial locations

Overseen By Clinical Trials Tessa

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Tessa Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids, Tumor vaccines, others

Disqualifiers: CNS involvement, Cardiovascular disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with relapsed or refractory classical Hodgkin lymphoma (cHL), a type of blood cancer that has returned or does not respond to standard treatments. The study tests a combination of two treatments: CD30.CAR-T (a therapy using modified immune cells) and nivolumab (a drug that helps the immune system attack cancer). The goal is to determine if this combination is safe and effective. Individuals whose cHL treatments have failed and who have a measurable cancerous lesion might be suitable candidates for this trial. 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 innovative therapy.

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

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude those on immunosuppressive drugs or chronic systemic corticosteroids.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CD30.CAR-T therapy is generally well-tolerated, with most patients handling it well. Studies have not found unexpected safety issues, and patients did not experience surprising or severe side effects. In some cases, side effects were mild, and the treatment showed promise in fighting tumors.

For nivolumab, research also suggests it is relatively safe for patients with Hodgkin lymphoma. Real-world data support its effectiveness, and there are no major safety concerns. Both treatments have been used in patients before, and while side effects can occur, previous studies indicate they are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Hodgkin Lymphoma, which typically involve chemotherapy and radiation, the combination of CD30.CAR-T cells and Nivolumab offers a novel approach. Researchers are excited because CAR-T therapy uses engineered T-cells to specifically target and destroy cancer cells expressing the CD30 protein, providing a highly personalized treatment option. Nivolumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This dual approach not only targets the cancer directly but also boosts the body's overall immune response, potentially leading to more durable remissions and fewer side effects compared to traditional therapies.

What evidence suggests that this combination therapy could be effective for Hodgkin Lymphoma?

Research has shown that autologous CD30.CAR-T therapy yields promising results for classical Hodgkin lymphoma (cHL). Studies report that 73.3% of patients experience a significant reduction in their tumors. Additionally, one study found that 39% of patients had no worsening of their disease for a year.

In this trial, participants will receive a combination of Nivolumab and CD30.CAR-T therapy. Nivolumab, a checkpoint inhibitor, has also proven effective in treating cHL. In one study, 92% of patients survived when it was used with chemotherapy, suggesting it can improve outcomes. Another study found that tumors completely disappeared in 14% of patients and shrank in others. This combination therapy shows promise for those with difficult-to-treat Hodgkin lymphoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Helen Heslop, MD

Principal Investigator

Baylor College of Medicine

Sairah Ahmed, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients aged 12+ with classical Hodgkin lymphoma (cHL) that didn't respond to standard treatments. They must have at least one lesion visible on PET-CT scans, good organ function, and a performance status indicating they can carry out daily activities with little or no assistance.

Inclusion Criteria

Anticipated life expectancy > 12 weeks

Signed ICF

My blood, kidney, liver, and clotting tests are within normal ranges.

Exclusion Criteria

I had a serious side effect from previous immunotherapy.

You are not currently taking any experimental drugs or tumor vaccines.

Evidence of active viral infection with hepatitis B virus (HBV)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Leukapheresis to produce CD30.CAR-T cells

1 week

Treatment

Participants receive 4 cycles of nivolumab and a single CD30.CAR-T infusion, preceded by lymphodepletion chemotherapy

16 weeks

Post-treatment Follow-up

Participants undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab

Up to 6 cycles of 28 days each

Long-term Follow-up

Participants are monitored for response assessments and safety until end of study, with additional safety monitoring and survival follow-up

Up to 15 years after Leukapheresis

What Are the Treatments Tested in This Trial?

Interventions

• Autologous CD30.CAR-T
• Nivolumab

Trial Overview The study tests a combination therapy of CD30.CAR-T cells and Nivolumab in cHL patients who haven't had success with first-line therapies. It's an early-phase trial assessing the safety and potential effectiveness of this new treatment approach.

How Is the Trial Designed?

Group I: Nivolumab and CD30.CAR-T Experimental Treatment 4 Interventions

Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).

Who Is Running the Clinical Trial?

Tessa Therapeutics

Lead Sponsor

Trials

4

Recruited

460+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study of 55 patients with relapsed/refractory Hodgkin's Lymphoma, Pembrolizumab showed a high response rate of 74.5%, with a complete response in 32.7% of patients, indicating its efficacy before autologous stem cell transplantation.

The 12-month overall survival rate was 92%, and the progression-free survival rate was 51%, demonstrating reasonable safety and promising survival outcomes for patients treated with checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. Halahleh, K., Al Sawajneh, S., Saleh, Y., et al.[2022]

Nivolumab, an immune checkpoint inhibitor targeting PD-1, has shown effectiveness in treating various cancers, including Hodgkin lymphoma, as evidenced by a partial response in a 75-year-old patient after multiple treatments.

The case highlights a potential risk where discontinuation of nivolumab led to the emergence and progression of new malignancies, suggesting that while ICIs can be effective, they may also uncover or allow the growth of other cancers in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two primary cancers appeared after discontinuation of nivolumab in the course of treating Hodgkin lymphoma: a case report. Potluri, LB., Nanjareddy, S., Al Sbihi, A., et al.[2023]

In a study of 21 patients with relapsed and refractory classic Hodgkin lymphoma who had previously failed nivolumab treatment, the combination of nivolumab and brentuximab vedotin showed a promising overall response rate of 57%.

The treatment was found to be relatively safe, with 63% of patients experiencing any grade adverse events, and only 10% experiencing severe (grade 3-4) adverse events, suggesting that this combination therapy could be a viable option for patients after PD-1 inhibitor failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma. Fedorova, LV., Lepik, KV., Volkov, NP., et al.[2023]

The addition of brentuximab vedotin and PD-1 inhibitors like nivolumab and pembrolizumab has improved treatment outcomes for patients with relapsed/refractory classical Hodgkin lymphoma, potentially leading to cures in some cases.

For patients unable to undergo intensive treatments, using a personalized approach with sequential therapies can extend survival while maintaining a reasonable quality of life, and participation in clinical trials for new therapies is encouraged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients. Mehta-Shah, N., Bartlett, NL.[2023]

In a study involving 51 patients with newly diagnosed advanced-stage classic Hodgkin lymphoma, nivolumab followed by a combination therapy (N-AVD) showed an impressive objective response rate of 84%, with 67% of patients achieving complete remission.

The treatment was generally well-tolerated, with 59% of patients experiencing grade 3 to 4 treatment-related adverse events, but most were manageable, and the 9-month modified progression-free survival rate was 92%, indicating strong efficacy and safety for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. Ramchandren, R., Domingo-Domènech, E., Rueda, A., et al.[2021]

In a phase 2 study involving 80 patients with relapsed classical Hodgkin's lymphoma, nivolumab demonstrated a high objective response rate of 66.3%, indicating its efficacy as a treatment option after failure of both autologous stem-cell transplantation and brentuximab vedotin.

Nivolumab was found to have an acceptable safety profile, with common side effects including fatigue and infusion-related reactions, and no treatment-related deaths reported, suggesting it is a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Younes, A., Santoro, A., Shipp, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11731380/

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... With the median follow-up range from 9.5 to 71.5 months, the 1-year PFS was 39% (95% CI 0.30–0.49, P = 0.04), and the 1-year OS was 89% (95% CI ...

2. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/7496/488598/Updated-Results-and-Correlative-Analysis

Autologous CD30.CAR-T-Cell Therapy in Patients with ... CAR-T therapy was well tolerated with no unexpected safety signal and showed excellent anti-tumor efficacy with an ORR of 73.3% in heavily ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04268706

Phase 2 Study Evaluating Autologous CD30.CAR-T Cells ... This is a two-part, Phase 2, multicenter, open-label, single arm study to evaluate the safety and efficacy of autologous CD30.CAR-T in adult and pediatric ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302624000644

Anti-CD30 CAR T cells as consolidation after autologous ... At a median follow-up of 48·2 months (IQR 27·5–60·7) post-infusion, the median progression-free survival for all treated patients (n=18) was 32·3 months (95% CI ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10394544/

Patient-reported outcomes in CD30-directed CAR-T cells ... We found an overall response rate of 62% in all evaluable patients. With a median follow-up of 533 days, the 1-year progression-free survival ...

6. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00064-4/abstract

Anti-CD30 CAR T cells as consolidation after autologous ... Anti-CD30 CAR T-cell infusion as consolidation after BEAM and autologous HSCT is safe, with low rates of toxicity and encouraging preliminary ...