Nivolumab + Ruxolitinib for Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Veronkia Bachanova

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Veronika Bachanova

Must not be taking: Immunosuppressants, Corticosteroids, CYP3A4 inhibitors

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

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a Phase I/II, multicenter, open-label, dose escalation/dose-expansion study to evaluate the tolerability, safety, and the maximum tolerated dose (MTD) of ruxolitinib when given with fixed dose nivolumab in patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

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.

What data supports the effectiveness of the drug Nivolumab for Hodgkin's Lymphoma?

Nivolumab has shown effectiveness in treating relapsed or refractory Hodgkin lymphoma, with studies indicating frequent and durable responses. It is approved in the USA for this condition, and its combination with other treatments like brentuximab vedotin has been explored for enhanced efficacy. ^{1 2 3 4 5}

Is the combination of Nivolumab and Ruxolitinib safe for treating Hodgkin's Lymphoma?

Nivolumab, used alone or with other treatments, has shown a generally acceptable safety profile in patients with Hodgkin's Lymphoma, with common side effects including fatigue, rash, and thyroid issues. Serious side effects like pneumonitis (lung inflammation) and neutropenia (low white blood cell count) can occur, but they are less common. Ruxolitinib's safety in combination with Nivolumab specifically for Hodgkin's Lymphoma isn't detailed here, but both drugs have been used safely in other contexts. ^{6 7 8 9 10}

How is the drug combination of Nivolumab and Ruxolitinib unique for treating Hodgkin's Lymphoma?

The combination of Nivolumab and Ruxolitinib is unique because Nivolumab is an immune checkpoint inhibitor that helps the immune system attack cancer cells, while Ruxolitinib is a JAK inhibitor that can reduce inflammation and potentially enhance the immune response. This combination may offer a novel approach by targeting different pathways compared to standard treatments. ^{1 3 4 11 12}

Research Team

Veronkia Bachanova

Principal Investigator

University of Minnesota

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Nivolumab (PD-1 Inhibitor)
• Ruxolitinib (JAK Inhibitor)

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.

Participant Groups

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 Canada, Switzerland for the following indications:

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Minnesota Minneapolis, MN

University of Iowa Hospitals and Clinics Iowa City, IA

University of Wisconsin Madison, WI

Who Is Running the Clinical Trial?

Veronika Bachanova

Lead Sponsor

Trials

1

Patients Recruited

50+

Incyte Corporation

Industry Sponsor

Trials

408

Patients Recruited

66,800+

Bristol-Myers Squibb

Industry Sponsor

Trials

2731

Patients Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Findings from Research

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]

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]

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]

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]

References

1. New Zealand 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. [2021]

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

Efficacy of Brentuximab Vedotin and Nivolumab in Refractory or Relapsed Hodgkin Lymphoma: A Systematic Review. [2022]

3. 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]

4. 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]

5. England 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. [2021]

6. Switzerland 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. [2020]

7. Germany 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Strategies for Recognizing and Managing Immune-Mediated Adverse Events in the Treatment of Hodgkin Lymphoma with Checkpoint Inhibitors. [2020]

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

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Final results of a phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. [2022]

12. 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]