CAR-T + Nivolumab for Hodgkin Lymphoma

(ACTION Trial)

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline 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.

What data supports the effectiveness of the treatment CAR-T + Nivolumab for Hodgkin Lymphoma?

Research shows that nivolumab, a part of this treatment, has been effective in treating relapsed or difficult-to-treat Hodgkin lymphoma, with a high response rate and durable effects. Additionally, combining similar drugs like brentuximab vedotin with nivolumab has shown impressive results, with many patients experiencing significant improvement. ^{1 2 3 4 5}

Is the combination of CAR-T and Nivolumab safe for treating Hodgkin Lymphoma?

Nivolumab, used alone, has shown an acceptable safety profile in patients with Hodgkin Lymphoma, with common side effects including fatigue, infections, and cough. Serious side effects occurred in 21% of patients, and there is a risk of immune-related issues like rash and thyroid problems. The safety of combining CAR-T with Nivolumab specifically needs further evaluation. ^{3 4 5 6 7}

How is the treatment CAR-T + Nivolumab for Hodgkin Lymphoma different from other treatments?

This treatment is unique because it combines CAR-T cell therapy, which uses modified immune cells to target cancer, with Nivolumab, a drug that helps the immune system recognize and attack cancer cells by blocking a protein called PD-1. This combination aims to enhance the immune response against Hodgkin Lymphoma, offering a novel approach compared to traditional chemotherapy or single-agent therapies. ^{3 8 9 10 11}

Research Team

Sairah Ahmed, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Helen Heslop, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. [2021]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Nivolumab for the Treatment of Relapsed or Progressive Classical Hodgkin Lymphoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. [2022]

8. China pubmed.ncbi.nlm.nih.gov

Two primary cancers appeared after discontinuation of nivolumab in the course of treating Hodgkin lymphoma: a case report. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Targeting the programmed cell death 1 pathway in Hodgkin lymphoma: the place of nivolumab. [2020]

10. Japan 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. [2023]

11. India pubmed.ncbi.nlm.nih.gov

Experience of Nivolumab Prior to Autologous Stem Cell Transplant for Relapsed Refractory Hodgkin Lymphoma. [2023]