Ipilimumab +/− Nivolumab for Hodgkin's Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Reid W Merryman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Anticancer therapies, Investigational agents

Disqualifiers: Autoimmune disease, Active infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug Ipilimumab works alone or with Nivolumab for individuals with classic Hodgkin's lymphoma that has returned or not responded to previous treatments. The research aims to determine if these drugs can slow down or stop the disease. Participants who have tried at least two other treatments, including a stem cell transplant, and still experience disease progression may be suitable for this study. Initially, participants will receive Ipilimumab alone and, depending on their response, may also receive a combination of Ipilimumab and Nivolumab. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on anticancer therapies or investigational agents close to the start of the study. Steroids are allowed if they are at a stable, low dose.

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

Research shows that Ipilimumab, used alone or with Nivolumab, is generally safe for patients with relapsed or refractory Hodgkin's lymphoma. Previous studies found that some patients experienced side effects, but these were usually manageable. Common side effects included fatigue and skin rashes, while serious side effects were less common.

The combination of Ipilimumab and Nivolumab has also been studied and is generally well-tolerated. Common side effects included skin reactions and itching, with serious side effects being infrequent.

These drugs are already approved for other conditions, such as certain types of cancer, indicating that their safety has been reviewed. However, individual reactions can vary, so consulting a healthcare provider is advisable when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy treatments for Hodgkin's Lymphoma, which often involve drugs like doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD regimen), ipilimumab and nivolumab target the immune system in a novel way. Researchers are excited about these treatments because they work by unleashing the body's own immune response against cancer cells. Ipilimumab blocks CTLA-4, a protein that normally keeps immune cells in check, while nivolumab targets the PD-1 pathway to prevent cancer cells from hiding from the immune system. This dual approach of using two checkpoint inhibitors could potentially lead to a more sustained and robust attack on the cancer, offering hope for better outcomes in patients who have not responded to traditional therapies.

What evidence suggests that this trial's treatments could be effective for Hodgkin's lymphoma?

Research shows that using Ipilimumab and Nivolumab together can help treat classic Hodgkin's lymphoma (cHL) that has returned or hasn't responded to other treatments. In this trial, participants will initially receive Ipilimumab alone. Depending on their response, they may continue with maintenance Ipilimumab or switch to a combination of Nivolumab and Ipilimumab, followed by maintenance Ipilimumab. Studies indicate that this combination can reduce the risk of the disease worsening or leading to death by 38% compared to using Nivolumab alone. Some patients have experienced long-lasting improvements, with the longest lasting over 23 months. When used alone, Ipilimumab prevented cancer progression for about 3.3 months on average. Overall, the combination of Ipilimumab and Nivolumab appears to be a promising option for patients with relapsed or refractory cHL. ^{1 2 6 7 8}

Who Is on the Research Team?

Reid W Merryman, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory classic Hodgkin's lymphoma, who have measurable disease and have progressed after two or more systemic treatments including a stem cell transplant if eligible. They must not have certain infections, severe allergies to monoclonal antibodies, recent major surgeries, uncontrolled medical conditions, active pneumonitis or colitis, other cancers within the last 2 years (with some exceptions), and should agree to use contraception.

Inclusion Criteria

My Hodgkin lymphoma diagnosis was confirmed through tissue examination.

My condition worsened after at least two treatments, including a stem cell transplant if I was eligible.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

I have had a stem cell transplant from a donor.

History of noncompliance to medical regimens

Other uncontrolled intercurrent illness that would limit adherence to study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ipilimumab Monotherapy

Participants receive Ipilimumab every 3 weeks for 4 cycles

12 weeks

4 visits (in-person)

Restaging Imaging

Participants undergo restaging imaging to assess response

1 week

Combination Therapy

Participants with stable or progressive disease receive Nivolumab and Ipilimumab every 3 weeks for 4 cycles

12 weeks

4 visits (in-person)

Maintenance Therapy

Participants receive maintenance Ipilimumab every 12 weeks for up to 8 cycles

up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Every 3 months for 2 years, then every 6 months for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The trial is testing the effectiveness of Ipilimumab alone versus in combination with Nivolumab for patients whose Hodgkin's lymphoma has returned or hasn't responded to treatment. It aims to see which approach is better at controlling the disease.

How Is the Trial Designed?

Group I: Disease Progression after previous therapy Experimental Treatment 2 Interventions

Participants will receive Ipilimumab alone and depending on response will receive either a maintenance course of Ipilimumab or a course of Nivolumab and Ipilimumab in combination followed by a maintenance course of Ipilimumab. Patients who have progressive disease after fewer than 4 cycles of ipilimumab are also eligible to proceed to combination therapy with nivolumab and ipilimumab, if they are clinically stable. * Ipilimumab Monotherapy: Every 3 weeks for 4 study cycles * Complete Response/Partial Response: Maintenance Ipilimumab every 12 weeks for 8 cycles * Stable or Progressive Disease Response: Nivolumab and Ipilimumab every 3 weeks for 4 study cycles, followed by Maintenance Ipilimumab every 12 weeks for 7 cycles

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

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]

Nivolumab, an antibody that enhances T-cell responses against tumors, was effective in achieving complete remission in a 65-year-old woman with refractory Hodgkin's lymphoma, despite her experiencing serious side effects like interstitial pneumonitis and cardiac hypokinesis after treatment.

The patient's cardiac function improved significantly after discontinuing Nivolumab and receiving appropriate management, highlighting the importance of monitoring and managing immune-related adverse events in patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced pneumonitis and cardiopathy in a patient with relapsed Hodgkin's lymphoma. Bonhomme-Faivre, L., Guarino, V., Misra, SC.[2023]

In a phase 1b trial involving 137 patients with relapsed/refractory lymphoid malignancies, the combination of nivolumab with ipilimumab or lirilumab showed significant activity in classical Hodgkin lymphoma, with overall response rates of 74% and 76%, respectively.

However, the combination therapies did not demonstrate a meaningful improvement in efficacy compared to single-agent nivolumab, and the combination with ipilimumab resulted in higher rates of severe treatment-related adverse events (29%) compared to lirilumab (15%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. Armand, P., Lesokhin, A., Borrello, I., et al.[2021]

In a phase 1/2 trial involving 64 patients with relapsed or refractory Hodgkin lymphoma, the combination of brentuximab vedotin with nivolumab showed a high overall response rate of 89%, indicating strong efficacy in treating this type of cancer.

The study also reported varying levels of treatment-related adverse events, with the triplet therapy group experiencing the highest rate of severe side effects (50%), highlighting the importance of balancing efficacy with safety in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Diefenbach, CS., Hong, F., Ambinder, RF., et al.[2021]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

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]

Nivolumab combined with ipilimumab significantly improves treatment outcomes in cancer, showing higher rates of complete response (CR), partial response (PR), and overall response rate (ORR) compared to either drug alone, based on a meta-analysis of 11 studies.

While the combination therapy N1I3 (1 mg/kg nivolumab and 3 mg/kg ipilimumab) was more effective than N3I1 (3 mg/kg nivolumab and 1 mg/kg ipilimumab), it also had a higher incidence of serious adverse events, though overall safety was still considered acceptable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis. Chen, J., Li, S., Yao, Q., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7737486/

Ipilimumab, Nivolumab and Brentuximab Vedotin in ... Although up to 80% of cHL patients are cured with first line therapy, treatment for patients with relapsed and refractory (R/R) cHL remains challenging; ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1669/531285/Ipilimumab-with-and-without-Nivolumab-in-Patients

Ipilimumab with and without Nivolumab in Patients with ... With a median follow-up of 11.5 months, the median progression-free survival for ipi monotherapy was 3.3 months. The duration of response for ...

3. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... The 90-month landmark OS rates were 32.9% vs. 22.0%, respectively. DOR: Median DOR was 82.8 months for patients treated with Opdivo plus Yervoy ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124044161

Ipilimumab with and without Nivolumab in Patients ... With a median follow-up of 11.5 months, the median progression-free survival for ipi monotherapy was 3.3 months. The duration of response for ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/607/500257/Results-from-an-Intergroup-Randomized-Phase-II

Results from an Intergroup Randomized Phase II Study of the ... In a planned analysis of patients with prior treatment with BV the CR rate was 25% in BV/N arm (2 of 8) and 60% in BV/N/I arm (3 of 5). The ...

6. news.bms.com news.bms.com/news/details/2022/Landmark-Five-Year-Data-from-Phase-3-CheckMate--227-Trial-Demonstrate-Long-Term-Durable-Survival-Outcomes-with-Opdivonivolumab-Plus-Yervoy-ipilimumab-in-First-Line-Treatment-of-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx

Landmark Five-Year Data from Phase 3 CheckMate -227 ... “With these results from CheckMate -227, we've now seen substantial increases in five-year survival rates compared to historical expectations ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6059238/

Hodgkin Lymphoma: Current Status and Clinical Trial ... Preliminary safety and efficacy data from the ongoing early-phase clinical trial investigating the combination of brentuximab vedotin with the immune checkpoint ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08762

Ipilimumab and Nivolumab for the Treatment of Relapsed ... This phase II trial investigates the effect of ipilimumab and nivolumab in treating patients with classic Hodgkin lymphoma that has come back (relapsed) or ...