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

33 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Nivolumab + CC-486 for treating Hodgkin's Lymphoma?

Nivolumab has shown effectiveness in treating Hodgkin's Lymphoma, as it is approved by the FDA for this condition and has demonstrated frequent and durable responses in relapsed/refractory cases. Additionally, it has been effective in combination therapies for relapsed or refractory Hodgkin lymphoma, suggesting potential benefits when used with other treatments like CC-486. ^{1 2 3 4 5}

Is the combination of Nivolumab and CC-486 safe for treating Hodgkin's Lymphoma?

Nivolumab, used for Hodgkin's Lymphoma, has shown some safety concerns, including immune-related side effects like myasthenia gravis (muscle weakness) and myositis (muscle inflammation). However, in studies, most side effects were mild, and the treatment was generally considered tolerable. ^{2 6 7 8 9}

How is the drug Nivolumab + CC-486 unique for treating Hodgkin's Lymphoma?

Nivolumab is a unique drug for Hodgkin's Lymphoma because it works by enhancing the body's immune response to cancer cells, specifically by blocking proteins that prevent the immune system from attacking tumors. This approach is different from traditional chemotherapy, as it uses the body's own defenses to fight the cancer. ^{1 2 3 10 11}

What is the purpose of this trial?

This trial tests a combination of a pill and an injection for patients with Hodgkin lymphoma that didn't respond to previous treatments or came back. The pill helps make healthy blood cells and kills bad ones, while the injection boosts the immune system to fight cancer. The injection is a type of treatment that was approved not long ago for Hodgkin lymphoma that has returned or worsened after a specific type of stem cell treatment.

Research Team

Matthew Mei, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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 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, 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

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]

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

Efficacy of Nivolumab and AVD in Early-Stage Unfavorable Classic Hodgkin Lymphoma: The Randomized Phase 2 German Hodgkin Study Group NIVAHL Trial. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. [2020]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Japan pubmed.ncbi.nlm.nih.gov

Association of CD8 + T cells expressing nivolumab-free PD-1 with clinical status in a patient with relapsed refractory classical Hodgkin lymphoma. [2023]

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

Nivolumab Treatment for Cancers in the HIV-infected Population. [2020]

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

Nivolumab-induced pneumonitis and cardiopathy in a patient with relapsed Hodgkin's lymphoma. [2023]

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

Population Pharmacokinetics and Exposure - Safety Analyses of Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. [2020]