What side effects are associated with this type of intervention?

Common treatments for Hodgkin's Lymphoma, particularly those involving immunotherapy with monoclonal antibodies like Nivolumab and hypomethylation agents like ASTX727, can have several side effects. Nivolumab is associated with immune-related adverse events such as colitis, pneumonitis, hepatitis, endocrinopathies, and skin reactions. ASTX727, which includes decitabine, can cause myelosuppression, gastrointestinal symptoms, and potential renal toxicity. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

For the treatment of Hodgkin's Lymphoma, the FDA has approved several immunotherapy drugs, including Nivolumab and Pembrolizumab, which are monoclonal antibodies targeting the PD-1 receptor to enhance the immune system's ability to fight cancer. Additionally, Brentuximab Vedotin, an antibody-drug conjugate targeting CD30, has been approved. While hypomethylation agents like Decitabine are more commonly used in other hematologic malignancies such as acute myeloid leukemia, their combination with immunotherapy, as seen in the trial with Nivolumab and ASTX727, represents an emerging area of research.

What other types of research exist?

Promising novel alternatives for Hodgkin's Lymphoma treatment in 2024 include: 1) Pembrolizumab (another PD-1 inhibitor) which has shown efficacy in various trials. 2) Brentuximab vedotin (an antibody-drug conjugate targeting CD30) which has been effective in relapsed or refractory cases. 3) CAR T-cell therapies targeting CD30, which are emerging as a potent option. 4) Bispecific antibodies like AFM13, targeting CD30 and CD16A, showing promising results in clinical trials.

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Hypomethylation Agent

Nivolumab + ASTX727 for B-Cell Lymphoma

Phase 1

Recruiting

Led By Catherine S Diefenbach

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status =< 2 (Karnofsky >= 80%)

Dose Expansion: Patients must have histologically confirmed relapsed or refractory DLBCL

Must not have

Pregnant women are excluded from this study because ASTX727 is a DNMTi agent and nivolumab is a PD-L1 inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ASTX727 and nivolumab, breastfeeding should be discontinued if the mother is treated with ASTX727 and nivolumab

Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome (GBS), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of nivolumab and ASTX727 in patients with B-cell lymphoma that has come back or is not responding to treatment. Nivolumab helps the immune system attack cancer, while ASTX727 enhances the effectiveness of another drug. The goal is to find a safe and effective dose for these patients.

Who is the study for?

Adults with relapsed or refractory B-cell lymphoma, including DLBCL, who have tried at least one other treatment and are not eligible for a transplant. They must be in relatively good health (ECOG/Karnofsky >=80%), have certain blood cell counts, no severe liver or kidney issues, and no uncontrolled illnesses. HIV-positive patients on effective therapy can join; those with hepatitis must be treated. Participants must agree to use effective contraception.

What is being tested?

The trial is testing the safety and optimal dosage of Nivolumab combined with ASTX727 (Decitabine and Cedazuridine) for B-cell lymphoma that's returned or hasn't responded to treatment. The goal is to see if this combo can help the immune system fight cancer better by stopping tumor growth.

What are the potential side effects?

Potential side effects include reactions related to the immune system attacking normal organs (autoimmune reactions), infusion-related reactions from receiving drugs through a vein, fatigue, digestive problems like stomach pain or constipation, changes in blood cells leading to increased infection risk or bleeding problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am mostly self-sufficient and can carry out daily activities.

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My DLBCL has returned or did not respond to treatment.

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My hepatitis B virus is undetectable with treatment.

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

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I am not on high-dose steroids or other immune-weakening medicines.

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My heart condition does not severely limit my daily activities.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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I am 18 years old or older.

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My B cell lymphoma has come back or did not respond to treatment.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant or breastfeeding.

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I do not have an active or history of severe autoimmune disease that could worsen.

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I was taken off anti-PD-1/PD-L1 or anti CTLA4 treatments due to side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Secondary study objectives

Complete response rate

Duration of response

Overall response rate

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (nivolumab, decitabine and cedazuridine)Experimental Treatment5 Interventions

Patients receive decitabine and cedazuridine PO QD on days 1-3 or 1-5 of each cycle and nivolumab IV over 30 minutes on day 15 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and collection of blood samples throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2030

Computed Tomography

2017

Completed Phase 2

~2790

Positron Emission Tomography

2011

Completed Phase 2

~2200

Nivolumab

2015

Completed Phase 3

~4010

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Hodgkin's Lymphoma include immunotherapy with monoclonal antibodies and hypomethylation agents. Immunotherapy, such as Nivolumab, works by enhancing the body's immune system to recognize and attack cancer cells. Monoclonal antibodies specifically target proteins on the surface of cancer cells, marking them for destruction by the immune system. Hypomethylation agents like Decitabine, often combined with cytidine deaminase inhibitors like Cedazuridine, work by reactivating tumor suppressor genes that have been silenced by abnormal DNA methylation, thereby inhibiting cancer cell growth. These treatments are crucial for Hodgkin's Lymphoma patients as they offer targeted approaches that can improve the effectiveness of the immune response and potentially lead to better outcomes with fewer side effects compared to traditional chemotherapy.