Nivolumab + CC-486 for Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Steroids, Live vaccines

Disqualifiers: Active CNS lymphoma, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for Hodgkin's lymphoma that hasn't responded to certain immunotherapies or has returned after treatment. It combines CC-486, a medication that aids in producing normal blood cells, with nivolumab (also known as Opdivo), an immunotherapy drug that helps the immune system attack cancer cells. The main goal is to determine the safest and most effective dose of CC-486 when used with nivolumab. Ideal participants are those who have tried other treatments for Hodgkin's lymphoma but still have the disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination 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. However, systemic steroid therapy for lymphoma symptom control must be reduced to 10 mg/day prednisone or equivalent. It's best to discuss your specific medications with the study team.

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

Research shows that the combination of CC-486 and nivolumab is under evaluation for safety in treating Hodgkin's lymphoma. Previous studies suggest this combination might be effective, but it remains early research.

For CC-486, some patients have experienced side effects like nausea and lower blood cell counts, though these vary among individuals. Nivolumab, an immunotherapy treatment, can cause side effects such as tiredness, skin reactions, or inflammation of organs, but many patients tolerate it well.

As a Phase 1 study, the primary goal is to assess the treatment's safety and determine the optimal dose. Researchers closely monitor any side effects. Since the trial is in Phase 1, more safety data is still being collected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Nivolumab with CC-486 for treating Hodgkin's Lymphoma because of its unique approach. Unlike standard treatments like chemotherapy or radiation, which directly attack cancer cells, Nivolumab is an immunotherapy that helps the body's immune system recognize and fight the cancer. CC-486 is an oral form of azacitidine, which can impact abnormal blood cell production and potentially enhance the immune response when used with Nivolumab. This combo not only targets the cancer more precisely but also offers a new way to engage the body's natural defenses, potentially leading to better outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for Hodgkin's Lymphoma?

In this trial, participants will receive a combination of CC-486 and Nivolumab. A previous study showed that CC-486 had a high success rate of 94.9% in patients with similar conditions, indicating a strong response to the treatment. CC-486 helps the body produce healthy cells and eliminate harmful ones. Nivolumab, which boosts the immune system, demonstrated a 92% survival rate when combined with chemotherapy for advanced Hodgkin's lymphoma. It enables the immune system to identify and attack cancer cells. Combining CC-486 with Nivolumab in this trial could enhance Nivolumab's effectiveness, offering hope for those with relapsed or hard-to-treat Hodgkin's lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew Mei, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults with classical Hodgkin lymphoma that's resistant to PD-1 therapy or has relapsed. They must have normal organ function, no severe allergies to nivolumab, and agree to use birth control. Excluded are those with recent transplants, certain autoimmune diseases, active infections, or a history of significant heart disease.

Inclusion Criteria

Hemoglobin >= 8 g/dL

My kidneys are working well enough, with a creatinine clearance of at least 40 mL/min.

I've had treatment before but can't have a stem cell transplant now.

Exclusion Criteria

I have not had a stroke or similar brain event in the last 6 months.

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures

I have had a solid organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine orally once daily on days 1-7 and nivolumab intravenously on day 8, repeated every 28 days for up to 24 cycles

Up to 24 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

1 visit at 30 days post-treatment, then every 12 weeks for 1 year, and every 24 weeks for another year

What Are the Treatments Tested in This Trial?

Interventions

• CC-486
• Nivolumab

Trial Overview The trial is testing the combination of CC-486 (oral azacitidine) and nivolumab for safety and effectiveness in treating Hodgkin lymphoma that hasn't responded to previous treatments. It aims to find the best dose while assessing how well this combo helps the immune system fight cancer.

How Is the Trial Designed?

Group I: Treatment (CC-486, nivolumab) Experimental Treatment 2 Interventions

Patients receive azacitidine PO QD on days 1-7 and nivolumab IV over 30 minutes on day 8. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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 case series of 16 people living with HIV who received nivolumab, 14% achieved complete responses, particularly notable in those with Hodgkin lymphoma, indicating potential efficacy similar to that seen in HIV-uninfected patients.

The study found that 40% of patients experienced immune-related adverse effects, with 27% developing pneumonitis, suggesting that while nivolumab can be effective, monitoring for side effects is crucial, especially in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Treatment for Cancers in the HIV-infected Population. Chang, E., Sabichi, AL., Kramer, JR., et al.[2020]

Nivolumab shows a favorable safety profile and a 65% objective response rate in patients with classical Hodgkin lymphoma, indicating its efficacy as a treatment option.

The study recommends a dosing regimen of 240 mg every 2 weeks, as it provides similar drug exposure to the previously used 3 mg/kg every 2 weeks, while maintaining safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure - Safety Analyses of Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. Wang, X., Ludwig, EA., Passarell, J., et al.[2020]

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 immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

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]

Citations

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Multicenter phase 2 study of oral azacitidine (CC-486) plus ... With the exception of anaplastic large cell lymphoma (ALCL), CHOP typically delivers a overall response rate (ORR) of 60% to 80%, complete response (CR) of 30% ...

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Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in ... Among the 59 patients evaluable for efficacy in both the escalation phase and expansion phase, the overall response rate (ORR) was 94.9% (95% CI ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119807097

A Phase I, Open Label, Multicenter Trial of Oral Azacitidine ... Grade 3/4 treatment-related AEs occurred in 21 (64%) pts; most common (≥10%) were neutropenia (58%) and febrile neutropenia (21%). Serious AEs (SAEs) occurred ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03703375?term=AREA%5BBasicSearch%5D(cell%20azacitidine%20celgene)&rank=7

Efficacy and Safety of Oral Azacitidine (CC-486) Compared ... This study is a multicentric, open-label, randomized phase 3 trial. The study will be conducted in select countries in Europe and South Korea sponsored by ...

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Real-world data of azacitidine for relapsed/refractory nodal ... Overall survival was 182 days. Five patients died from progressive disease; three were in complete remission after allogeneic stem cell transplantation; two ...

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The Combination of Nivolumab and CC-486 Is Active in ... Therefore, we conducted a phase I study evaluating the safety and efficacy of nivolumab and CC-486, an oral HMA, in pts with RR HL refractory to ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-13436

CC-486 and Nivolumab for the Treatment of Hodgkin ... This phase I trial tests the safety and best dose of CC-486 (an oral form of azacitidine) when given together with nivolumab in treating patients with ...

8. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05162976?keyword=%22Classic%20Hodgkin%20Lymphoma%22

CC-486 and Nivolumab for the Treatment of Hodgkin ... PRIMARY OBJECTIVES:~I. Evaluate the safety and tolerability of a regimen combining oral azacitidine (CC-486) and nivolumab in patients with Hodgkin lymphoma ...

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Efficacy, Safety, and Biomarkers of Response to Azacitidine ... This study was designed to assess whether the addition of nivolumab to azacitidine was safe and effective. Results. Patient Characteristics and Treatments.

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Advances in Hodgkin Lymphoma Treatment The NIVAHL trial investigated the combination of nivolumab plus AVD (N-AVD) in early-stage cHL patients with unfavorable disease by GHSG criteria, with ...