CC-486 and Nivolumab for the Treatment of Hodgkin Lymphoma Refractory to PD-1 Therapy or Relapsed

NCT05162976 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 21319P30CA033572NCI-2021-13436
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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 Hodgkin lymphoma that does not respond (refractory) to PD1-based immunotherapy or has come back (relapsed). CC-486 is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CC-486 in combination with nivolumab may render nivolumab more effective.

Conditions

Recurrent Classic Hodgkin Lymphoma; Refractory Classic Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity

  Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (\[CTCAE\], version 5.0).

  Up to 28 days (1 cycle)

• Overall response rate (ORR)

  Defined as the proportion of patients that have a documented complete response (CR) or particle response (PR) at any time during study treatment. Will be estimated by the proportion of response-evaluable patients achieving CR or PR along with the 95% exact binomial confidence interval.

  Up to 2 years

Secondary Outcomes (5)

• Complete response (CR) rate

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

• Overall survival (OS)

  Time from initiation of study therapy to death from any cause, assessed up to 2 years

• Progression-free survival (PFS)

  Time from initiation of study therapy to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 2 years

• Incidence of adverse events

  Up to 30 days after last dose

Study Arms (1)

Treatment (CC-486, nivolumab)

EXPERIMENTAL

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.

Biological: Nivolumab; Drug: Oral Azacitidine

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (CC-486, nivolumab)

Oral Azacitidine DRUG

Given PO

Also known as: CC-486

Treatment (CC-486, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from archival tissue of a biopsy that was performed after the most recent systemic therapy
• Exception may be granted by the principal investigator (PI) if a biopsy is not feasible and/or safe
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Histologically confirmed diagnosis of classical Hodgkin lymphoma (excluding nodular lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
• Refractory to PD-1/PD-L1 directed immunotherapy, defined as patients who had prior exposure to PD-1/PD-L1 immunotherapy and either:
• Achieved a best response of PD, or
• Achieved a best response of CR/PR but developed PD while on active PD-1/PD-L1 treatment or within 12 weeks of last dose of PD-1/PD-L1 treatment
• Relapse must have been confirmed histologically (with hematopathology review at the participating institution)
• Exceptions may be granted with study PI approval
• Patient must have received at least one prior systemic therapy and must not currently be candidate for stem cell transplantation
• Measurable disease by computed tomography (CT) or positron emission tomography (PET)/CT scan with one or more sites of disease \>= 1.5 cm in longest dimension
• Fully recovered from the acute toxic effects (except alopecia) to =\< Grade 1 to prior anti-cancer therapy

You may not qualify if:

• Prior allogeneic stem cell transplant within 6 months prior to day 1 of protocol therapy
• If prior allogeneic transplant, then no active graft-versus-host disease (GVHD), no systemic immunosuppression for at least 3 months prior to study enrollment, and no history of grade 3-4 acute GVHD
• Autologous stem cell transplant within 3 months prior to day 1 of protocol therapy
• Prior solid organ transplant
• Systemic steroid therapy for lymphoma symptom control must be tapered down to =\< 10 mg/day prednisone or equivalent
• Live vaccine within 30 days prior to day 1 of protocol therapy
• Concomitant investigational therapy
• History of prior \>= grade 3 hypersensitivity to nivolumab, or history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents or to any of the excipients, including mannitol
• Known active central nervous system (CNS) involvement by lymphoma
• History of active pneumonitis or interstitial lung disease requiring supplemental oxygen or corticosteroid treatment
• History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
• History of another primary malignancy that has not been in remission for at least 2 years, with the following exceptions:
• Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
• Adequately treated in situ carcinomas (e.g. cervical, esophageal) without evidence of disease
• Asymptomatic prostate cancer managed with a watch-and-wait strategy

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Interventions

Nivolumab; Azacitidine; cc-486

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Matthew Mei, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: December 20, 2021
• Study Start: January 3, 2022
• Primary Completion (Estimated): May 12, 2026
• Study Completion (Estimated): May 12, 2026
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

US (1)