What side effects are associated with this type of intervention?

The most common treatments for Hodgkin's Lymphoma, such as demethylation agents (e.g., CC-486) and monoclonal antibody immunotherapies (e.g., Nivolumab), have distinct side effect profiles. Demethylation agents can cause nausea, vomiting, diarrhea, fatigue, and low blood cell counts, increasing infection risk. Nivolumab, a PD-1 inhibitor, can lead to immune-related side effects like pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions due to its mechanism of enhancing the immune system, which can sometimes target normal tissues.

What prior FDA approvals exist?

Nivolumab, a monoclonal antibody that targets PD-1, has been FDA-approved for the treatment of classical Hodgkin's Lymphoma, particularly in patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin. Another similar immunotherapy drug, Pembrolizumab, which also targets PD-1, has received FDA approval for the treatment of relapsed or refractory classical Hodgkin's Lymphoma. While there are no specific FDA approvals for demethylation agents like CC-486 in Hodgkin's Lymphoma, hypomethylating agents such as azacitidine have been explored in clinical trials for their potential benefits in various hematologic malignancies.

What other types of research exist?

Promising alternatives to CC-486 and Nivolumab for Hodgkin's Lymphoma include Brentuximab Vedotin, which has shown efficacy in combination with Nivolumab for patients ineligible for cytotoxic chemotherapy, and other immune checkpoint inhibitors like Pembrolizumab, which has been used in various cancers and may offer benefits in Hodgkin's Lymphoma. Additionally, novel combinations and regimens tailored to individual patient profiles, such as those involving targeted therapies or other monoclonal antibodies, should be considered.

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Demethylation Agent

Nivolumab + CC-486 for Hodgkin's Lymphoma

Phase 1

Waitlist Available

Led By Matthew Mei, MD

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

Creatinine clearance of >= 40 mL/min per 24 hour urine test or the Cockcroft-Gault formula

Patient must have received at least one prior systemic therapy and must not currently be a candidate for stem cell transplantation

Must not have

Prior solid organ transplant

History of progressive multifocal leukoencephalopathy (PML)

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 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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at the infusion site, fatigue, digestive issues like nausea or diarrhea, blood cell count changes increasing infection risk, potential liver inflammation indicated by elevated enzymes levels in tests.

Eligibility Criteria

Inclusion Criteria

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

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

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

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I can perform all my self-care but may not be able to do heavy physical work.

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My diagnosis is classical Hodgkin lymphoma, not the nodular type, confirmed by a specialist.

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I am 18 years old or older.

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I have recovered from side effects of cancer treatment, except for hair loss.

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My blood clotting tests are within normal limits, or if I'm on blood thinners, they're properly adjusted.

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I have a tumor that is larger than 1.5 cm, confirmed by a CT or PET/CT scan.

Exclusion Criteria

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

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I have had a solid organ transplant.

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I have had progressive multifocal leukoencephalopathy in the past.

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I have had lung inflammation or disease needing extra oxygen or steroids.

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I have an active hepatitis B or C infection.

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I have a history of serious gut conditions that could affect drug absorption or increase risk of gut side effects.

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My lymphoma has spread to my brain or spinal cord.

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I am not pregnant or breastfeeding.

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I am taking 10 mg or less of prednisone daily for my lymphoma.

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I do not have any uncontrolled serious illnesses.

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I had a stem cell transplant using my own cells within the last 3 months.

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I have an active HIV infection.

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I have not received a live vaccine in the last 30 days.

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I have been diagnosed with an immune system disorder.

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I do not have any uncontrolled infections.

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

Dose-limiting toxicity

Overall response rate (ORR)

Secondary study objectives

Complete response (CR) rate

Duration of response (DOR)

Incidence of adverse events

+2 more

Side effects data

From 2023 Phase 3 trial • 216 Patients • NCT01566695

76%

Nausea

68%

Diarrhoea

63%

Vomiting

49%

Neutropenia

47%

Constipation

28%

Pyrexia

27%

Thrombocytopenia

27%

Febrile neutropenia

27%

Oedema peripheral

26%

Epistaxis

25%

Decreased appetite

23%

Asthenia

21%

Fatigue

20%

Petechiae

18%

Anaemia

15%

Cough

14%

Contusion

13%

Abdominal pain

12%

Dyspnoea

12%

Back pain

11%

Urinary tract infection

11%

Hypokalaemia

Leukopenia

Weight decreased

Insomnia

Pneumonia

Mouth haemorrhage

Hypomagnesaemia

Haematoma

Anxiety

Alanine aminotransferase increased

Arthralgia

Sepsis

Dizziness

Gingival bleeding

Upper respiratory tract infection

Pain in extremity

Depression

Confusional state

Septic shock

Gastrooesophageal reflux disease

Cellulitis

Oral herpes

Serum ferritin increased

Hyperglycaemia

Iron overload

Ecchymosis

Hypotension

Neutropenic sepsis

Fall

Lung infection

General physical health deterioration

Cardiac failure congestive

Tachyarrhythmia

Bone marrow failure

Cardiac failure

Multiple organ dysfunction syndrome

Cholecystitis

Hyperbilirubinaemia

Atypical pneumonia

Bronchopulmonary aspergillosis

Subdural haematoma

Haemorrhage intracranial

Acute kidney injury

Renal failure

Febrile infection

Gastroenteritis

Myocardial infarction

Corona virus infection

Gastritis

Pancytopenia

Abdominal pain upper

Epididymitis

Escherichia sepsis

Prerenal failure

Renal colic

Chronic kidney disease

Lethargy

Groin abscess

Lower respiratory tract infection

Device related infection

Influenza

Klebsiella infection

Haemolytic anaemia

Haemorrhagic anaemia

Acute myocardial infarction

Angina unstable

Atrial fibrillation

Gastrointestinal haemorrhage

Intestinal obstruction

Intestinal perforation

Neutropenic colitis

Oesophageal achalasia

Oral mucosal blistering

Rectal haemorrhage

Gait disturbance

Hypothermia

Abscess limb

Arteriovenous fistula site infection

Klebsiella sepsis

Meningitis

Meningitis bacterial

Myringitis

Pneumonia fungal

Pneumonia pneumococcal

Pseudomonal sepsis

Pulmonary mycosis

Respiratory tract infection

Skin infection

Staphylococcal infection

Urinary tract infection bacterial

Viral sepsis

Periorbital haematoma

Febrile nonhaemolytic transfusion reaction

Head injury

Hip fracture

Subdural haemorrhage

Upper limb fracture

Dehydration

Diabetes mellitus inadequate control

Diabetic metabolic decompensation

Hyperkalaemia

Hypoglycaemia

Muscular weakness

Polychondritis

Acute myeloid leukaemia

Bone neoplasm

Bowen's disease

Colon adenoma

Mantle cell lymphoma recurrent

Spinal cord neoplasm

Central nervous system lesion

Transient ischaemic attack

Epilepsy

Generalised tonic-clonic seizure

Acute respiratory distress syndrome

Pleural effusion

Pleurisy

Pneumonia aspiration

Pulmonary embolism

Respiratory failure

Hypersensitivity vasculitis

Rash

Rash generalised

Shock haemorrhagic

Cardiogenic shock

Intra-abdominal haemorrhage

Status epilepticus

Syncope

Urinary retention

Prostatitis

100%

80%

60%

40%

20%

Study treatment Arm

Oral Azacitidine Plus Best Supportive Care

Placebo Plus Best Supportive Care

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 (CC-486, nivolumab)Experimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Oral Azacitidine

2013

Completed Phase 3

~950

Nivolumab

2015

Completed Phase 3

~4010

0 / 22Eligibility 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

Demethylation agents, like CC-486, inhibit DNA methyltransferases, leading to hypomethylation and reactivation of tumor suppressor genes, promoting cancer cell apoptosis. Monoclonal antibody immunotherapy, such as Nivolumab, blocks the PD-1 receptor on T-cells, preventing cancer cells from evading the immune system and enhancing immune response against the tumor. These targeted mechanisms are vital for Hodgkin's Lymphoma patients as they disrupt cancer cell survival and boost immune-mediated tumor destruction.