Nivolumab + Ruxolitinib for Hodgkin's Lymphoma

Recruiting at 2 trial locations

Overseen By Ahran Lee

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Veronika Bachanova

Must not be taking: Immunosuppressants, Corticosteroids, CYP3A4 inhibitors

Disqualifiers: Pregnancy, CNS involvement, Cardiovascular disease, Autoimmune disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments: nivolumab (an immunotherapy drug) and ruxolitinib (a JAK inhibitor) for individuals with classical Hodgkin's lymphoma that hasn't responded to other treatments. The goal is to determine the safety of this combination and identify the optimal dose. Individuals who have tried at least two other therapies but still have measurable disease might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination.

Will I have to stop taking my current medications?

The trial requires a 1-week washout period (time without taking certain medications) for those currently on strong CYP3A4 inhibitors or Fluconazole over 200 mg/day. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research has shown that the combination of nivolumab and ruxolitinib is generally well-tolerated. In earlier studies, most side effects were mild to moderate, classified as grade 1 or 2. A few patients required hospitalization, with two cases of pneumonia and one due to disease-related reasons. This indicates that while the treatment is mostly safe, some risks exist.

Ruxolitinib alone has been shown to be safe, although its benefits for Hodgkin's lymphoma were limited. When combined with nivolumab, the treatment appears more effective for some patients, especially those unresponsive to other treatments. Overall, the treatment is considered safe, but like all medical treatments, it may have some side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining nivolumab and ruxolitinib for treating Hodgkin's Lymphoma because this duo targets the disease in a novel way. Unlike traditional chemotherapies that attack rapidly dividing cells broadly, nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. Ruxolitinib, typically used for blood disorders, is a JAK inhibitor that can reduce inflammation and potentially enhance the immune response. Together, they offer a targeted approach that could lead to better outcomes with fewer side effects compared to standard treatments like ABVD chemotherapy or radiation therapy.

What evidence suggests that Nivolumab and Ruxolitinib could be effective for Hodgkin's Lymphoma?

Research has shown that using nivolumab with ruxolitinib may be promising for treating Hodgkin's lymphoma. In studies, 54% of patients responded to this combination, and in six out of 19 patients, the cancer became undetectable. This trial will evaluate the combination of ruxolitinib and nivolumab, with participants receiving ruxolitinib orally twice daily and nivolumab intravenously every four weeks. This treatment has also benefited patients who did not improve with previous immunotherapy. Ruxolitinib blocks a protein called JAK, which is related to the immune response, enhancing the effectiveness of nivolumab, a drug that enables the immune system to attack cancer cells. These findings suggest this combination could be a strong option for those with relapsed or hard-to-treat Hodgkin's lymphoma. ^{5 6 7 8 9}

Who Is on the Research Team?

Veronkia Bachanova

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adults over 18 with classical Hodgkin lymphoma that's come back or hasn't responded to treatment, including checkpoint inhibitors. They must have measurable disease, be in fair health (ECOG 0-2), and have normal organ function tests. Participants need prior treatments like chemotherapy and possibly a transplant but should be recovered from these treatments. Women of childbearing age must test negative for pregnancy, and sexually active participants must use contraception.

Inclusion Criteria

I've had treatment with checkpoint inhibitors and my cancer either got worse, stayed the same, or partially improved.

I have tried at least 2 treatments including chemotherapy and transplantation without success.

Written informed consent and HIPAA authorization for release of personal health information

Exclusion Criteria

My lymphoma affects my brain or spinal cord.

I have heart problems that are not well-managed.

I am currently taking immunosuppressive drugs, including steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Participants receive ruxolitinib at their assigned dose taken orally twice daily on a 28-day cycle combined with nivolumab 480 mg IV administered every 4 weeks until disease progression, unacceptable toxicity, or for a maximum of 2 years.

Up to 24 months

Monthly visits for IV administration

Treatment Phase II

Participants receive ruxolitinib at 20mg orally twice daily on a 28-day cycle combined with nivolumab 480 mg IV administered every 4 weeks until disease progression, unacceptable toxicity, or for a maximum of 2 years.

Up to 24 months

Monthly visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Ruxolitinib

Trial Overview The trial is testing the combination of Ruxolitinib with Nivolumab to find the highest dose patients can take without severe side effects (MTD). It's an early-phase study where everyone gets both drugs at varying doses to see how well they work together against relapsed or refractory classical Hodgkin lymphoma.

How Is the Trial Designed?

Group I: Phase II: Ruxolitinib and Nivolumab Experimental Treatment 2 Interventions

Participants will receive ruxolitinib at 20mg orally twice daily on a 28-day cycle combined with nivolumab 480 mg IV administered every 4 weeks (i.e. on Day 1 of a 28-day cycle) until disease progression, unacceptable toxicity, or for a maximum of 2 years.

Group II: Phase I:Ruxolitinib and Nivolumab Experimental Treatment 2 Interventions

Participants will receive ruxolitinib at their assigned dose taken orally twice daily on a 28-day cycle combined with nivolumab 480 mg IV administered every 4 weeks (i.e. on Day 1 of a 28-day cycle) until disease progression, unacceptable toxicity, or for a maximum of 2 years.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Veronika Bachanova

Lead Sponsor

Trials

1

Recruited

50+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

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 is an effective immune checkpoint inhibitor for treating various cancers, including melanoma and non-small-cell lung cancer, and its efficacy may be linked to the expression of PD-L1 in tumors.

In comparing two antibodies for detecting PD-L1, the 28-8 antibody showed superior detection capabilities over E1L3N, highlighting the importance of antibody choice and detection methods in assessing PD-L1 expression for predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Analytical Comparison of Dako 28-8 PharmDx Assay and an E1L3N Laboratory-Developed Test in the Immunohistochemical Detection of Programmed Death-Ligand 1. Cogswell, J., Inzunza, HD., Wu, Q., et al.[2021]

In a retrospective analysis of 66 patients with relapsing refractory classical Hodgkin's lymphoma (cHL) treated with PD-1 inhibitors, the overall response rate was 70%, with 47% achieving complete remission and 23% partial remission, indicating strong efficacy in a real-world setting.

The treatment was well-tolerated, with immune-related adverse events mostly being mild (grades 1-2), and no deaths attributed to the therapy, suggesting a favorable safety profile alongside a median overall survival of 65% at 5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world analysis of PD1 blockade from the Rete Ematologica Pugliese (REP) in patients with relapse/refractory Hodgkin's lymphoma. Gaudio, F., Loseto, G., Bozzoli, V., 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]

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 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]

In a phase II study involving 17 Japanese patients with relapsed or refractory classical Hodgkin lymphoma, nivolumab demonstrated a high overall response rate of 87.5% and a disease control rate of 93.8%, indicating its efficacy in this patient population.

Nivolumab was generally well-tolerated, with no grade 5 adverse reactions reported; however, monitoring for late-onset pulmonary toxicities is recommended, as some patients experienced these effects after 17 months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Maruyama, D., Terui, Y., Yamamoto, K., et al.[2022]

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]

Nivolumab and pembrolizumab are effective PD-1 checkpoint inhibitors for treating relapsed or refractory classical Hodgkin lymphoma, with FDA approval based on their substantial therapeutic activity and acceptable safety profile in heavily pretreated patients.

Patients receiving these therapies should be closely monitored for immune-mediated adverse events (IMAEs), as they can lead to serious complications like pneumonitis and colitis; early recognition and management of these events are crucial for maintaining treatment efficacy and patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for Recognizing and Managing Immune-Mediated Adverse Events in the Treatment of Hodgkin Lymphoma with Checkpoint Inhibitors. Vardhana, S., Cicero, K., Velez, MJ., et al.[2020]

In a study of 30 patients with untreated classic Hodgkin lymphoma, the combination of pembrolizumab with chemotherapy (AVD) demonstrated a 100% overall response rate and a 90% complete response rate, indicating high efficacy.

The treatment was generally safe, with no significant delays in administration; however, some patients experienced serious adverse events, including febrile neutropenia and immune-related effects, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. Lynch, RC., Ujjani, CS., Poh, C., et al.[2023]

Brentuximab vedotin (BV) and nivolumab (NV) have shown high response rates as monotherapies for refractory or relapsed classical Hodgkin lymphoma (RRHL), although there is still a risk of disease progression.

Combining BV or NV with chemotherapy may enhance treatment effectiveness and serve as a bridge to hematopoietic stem cell transplantation, potentially leading to better survival rates for patients with RRHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Brentuximab Vedotin and Nivolumab in Refractory or Relapsed Hodgkin Lymphoma: A Systematic Review. Macapagal, SC., Lee, H., Abdul Jabbar, J., et al.[2022]

Nivolumab and pembrolizumab, both anti-PD-1 therapies, show promising efficacy in treating relapsed or refractory lymphoma, with an overall response rate of 58% and a 6-month overall survival rate of 96% across 10 studies involving 718 patients.

While both treatments have tolerable adverse effects, pembrolizumab is associated with fewer instances of fatigue and rash compared to nivolumab, and patients with Hodgkin lymphoma respond better to treatment than those with non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails. Zhou, H., Fu, X., Li, Q., et al.[2020]

In a phase II study involving 17 Japanese patients with relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin, nivolumab demonstrated a high objective response rate (ORR) of 81.3%, indicating strong efficacy as a treatment option.

Nivolumab was found to be generally well-tolerated, with most adverse events being mild (grade 1 or 2), although 23.5% of patients experienced more severe (grade 3 or 4) adverse events, suggesting it has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Maruyama, D., Hatake, K., Kinoshita, T., et al.[2022]

Citations

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Combining JAK Inhibitors with Immune Checkpoint Inhibitors Complete responders to ruxolitinib plus nivolumab combination therapy demonstrated significantly greater reductions in both neutrophil‐to‐ ...

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/jak-inhibitor-improves-cancer-immunotherapy

Drug Combo JAKs Up Immunotherapy in Two Clinical Trials In contrast, 2-year progression-free survival was 23% in a small clinical trial of people with lymphoma who received nivolumab and another drug ...

3. nature.com nature.com/articles/s41392-024-01968-0

improved response through combination with JAK inhibition For 19 patients with the combined treatment, an overall response rate of 54% was achieved, and six patients showed a complete metabolic response ...

4. science.org science.org/doi/10.1126/science.ade8520

JAK inhibition enhances checkpoint blockade ... A combination of ruxolitinib and nivolumab resulted in improved clinical efficacy in patients who had previously failed checkpoint blockade immunotherapy.

5. journals.lww.com journals.lww.com/oncology-times/fulltext/2024/09000/ruxolitinib_enhances_immunotherapy_in_hodgkin.25.aspx

Ruxolitinib Enhances Immunotherapy in Hodgkin Lymphoma A Scripps Research team found the JAK inhibitor ruxolitinib rescued the function of exhausted T cells and enhanced the efficacy of immune checkpoint blockade ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10515879/

Incorporation of Ruxolitinib in the Management ... The reported data suggest that ruxolitinib has a modest short-lived, and limited potential in HL patients, with a highly acceptable safety profile. Additional ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121022278

Ruxolitinib Plus Nivolumab in Patients with R/R Hodgkin ... The combination was well tolerated; most AEs were grade 1 and 2. Only 3 patients required hospitalization (2 had pneumonia, one for disease ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03681561

NCT03681561 | Nivolumab With Ruxolitinib in Relapsed or ... This is a Phase I/II, multicenter, open-label, dose escalation/dose-expansion study to evaluate the tolerability, safety, and the maximum tolerated dose ...

9. ashpublications.org ashpublications.org/hematology/article/2023/1/510/506454/The-optimal-management-of-relapsed-and-refractory

The optimal management of relapsed and refractory Hodgkin ... A phase 1/2 trial in 19 evaluable patients with relapsed/refractory cHL after prior CPI therapy was well tolerated and demonstrated an ORR of 39 ...