What side effects are associated with this type of intervention?

Common treatments for Hodgkin's Lymphoma, such as the ABVD chemotherapy regimen, can cause side effects like nausea, vomiting, hair loss, fatigue, and increased infection risk due to bone marrow suppression. Specific drugs in ABVD can also lead to lung toxicity (Bleomycin) and heart damage (Adriamycin). Nivolumab, a PD-1 inhibitor, can cause immune-related side effects including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions, with severe cases potentially leading to severe pneumonitis and myocarditis.

What prior FDA approvals exist?

Nivolumab, a PD-1 inhibitor, has been studied for its efficacy in treating Hodgkin's Lymphoma, particularly in patients with abnormal PET scans after two cycles of ABVD. This aligns with the broader use of immune checkpoint inhibitors in oncology. Pembrolizumab, another PD-1 inhibitor, has also been approved for various cancers, including Hodgkin's Lymphoma, especially for patients who have relapsed or are refractory to other treatments. These approvals highlight the growing role of immunotherapy in managing Hodgkin's Lymphoma.

What other types of research exist?

Promising novel alternatives to Nivolumab for Hodgkin's Lymphoma patients include Pembrolizumab (another PD-1 inhibitor), Brentuximab Vedotin (an antibody-drug conjugate targeting CD30), and combination therapies involving checkpoint inhibitors with other agents such as chemotherapy or targeted therapies. These alternatives have shown efficacy in clinical trials and are considered viable options for treatment.

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Anti-tumor antibiotic

A(B)VD + Nivolumab for Hodgkin's Lymphoma

Q: What is the mechanism of action of this treatment?

The most common treatments for Hodgkin's Lymphoma include ABVD chemotherapy and immune checkpoint inhibitors like Nivolumab. ABVD, which stands for Adriamycin, Bleomycin, Vinblastine, and Dacarbazine, works by damaging the DNA of cancer cells, thereby preventing them from dividing and growing. Nivolumab, on the other hand, is a PD-1 inhibitor that blocks the programmed cell death protein 1 (PD-1) pathway, which cancer cells often exploit to evade the immune system. By inhibiting this pathway, Nivolumab helps the immune system recognize and attack cancer cells more effectively. These treatments are crucial for Hodgkin's Lymphoma patients as they target the cancer cells directly and enhance the body's immune response, thereby improving the chances of remission and cure.

Phase 1 & 2

Waitlist Available

Led By Alison Moskowitz, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Age ≥ 18

Serum creatinine ≤ 1.5 x Upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (measured using the Cockcroft-Gault formula

Must not have

Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

A left-ventricular ejection fraction < 50%

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if adding Nivolumab to standard chemotherapy (ABVD) can improve cure rates for high-risk Hodgkin lymphoma patients. It targets those with advanced stages of the disease who haven't been treated yet. Nivolumab helps the immune system fight cancer, while ABVD kills cancer cells. Nivolumab is well tolerated and highly effective in relapsed/refractory classic Hodgkin lymphoma but has not been adequately studied in patients who are receiving their initial treatment for this type of cancer.

Who is the study for?

This trial is for adults with untreated classical Hodgkin lymphoma who are at higher risk (stage III or IV, or positive PET scans after initial treatment). It's open to those under 60 for one cohort and over 60 for another. Participants need functioning major organs, not be pregnant or breastfeeding, and must use reliable birth control.

What is being tested?

The study is testing the effectiveness of Nivolumab combined with a chemotherapy regimen called ABVD (which includes dacarbazine, doxorubicin, bleomycin, vinblastine) as a first-line treatment to see if it can improve cure rates in patients with high-risk Hodgkin lymphoma.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in various organs due to Nivolumab. Chemotherapy drugs may cause nausea, hair loss, fatigue, increased infection risk and heart complications among other side effects.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My kidney function, measured by creatinine levels, is within the normal range.

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I have been diagnosed with classical Hodgkin lymphoma.

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My condition is in an advanced stage, specifically Ann Arbor Stage III or IV.

Exclusion Criteria

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

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I haven't had active cancer in the last 3 years, except for certain curable types.

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My heart's pumping ability is below normal.

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I do not have uncontrolled heart problems.

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I have tested positive for HIV/AIDS.

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I have active brain or leptomeningeal metastases.

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I have been diagnosed with nodular lymphocyte-predominant Hodgkin's lymphoma.

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I have severe heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 year

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

Treatment Details

Study Objectives

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

Primary study objectives

Phase II- progression free survival

number of patients who have dose limiting toxicity

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: < 60 years of age with advanced stage (HL) untreatedExperimental Treatment5 Interventions

The study will employ a 3+3 design and include 3 treatment cohorts. In each cohort, patients will receive 6 cycles of A(B)VD and 8 doses of nivolumab. In dose level 1, patients will receive nivolumab in combination with AVD during cycle 6 only followed by 6 additional doses of nivolumab. In subsequent dose levels, nivolumab will be combined with increasing numbers of cycles of AVD. Based upon safety data from another study with Nivolumab, we will no longer need to evaluate dose level 2. If we determine that dose level 1 is safe, the next group of patients will enroll onto dose level 3. A PET scan will be performed after 2 cycles of ABVD and those with a PET-negative response (defined by Deauville 1, 2 or 3) will proceed with 4 additional cycles of ABVD or AVD (per treating physician preference).

Group II: 60 years of age and older with HL (any stage) untreatedExperimental Treatment4 Interventions

The study will employ a 3+3 design and include 3 treatment cohorts. In each cohort, patients will receive 6 cycles of AVD and 12 doses of nivolumab. In this cohort, patients will receive nivolumab in combination with AVD during cycles 5 and 6 only, followed by 8 additional doses of nivolumab. In subsequent cohorts, nivolumab will be combined with increasing numbers of cycles of AVD. Based upon safety data from another study with Nivolumab, we will no longer need to evaluate dose level 2. If we determine that dose level 1 is safe, the next group of patients will enroll onto dose level 3. Prophylactic growth factor support is mandatory for all patients on Cohort B and should be used per the treating physician's discretion for all other patients.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

doxorubicin

2005

Completed Phase 3

~9130

dacarbazine

2008

Completed Phase 3

~6240

Bleomycin

2001

Completed Phase 3

~5100

vinblastine

2010

Completed Phase 3

~1490

Nivolumab

2014

Completed Phase 3

~5220

0 / 11Eligibility 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 ABVD chemotherapy and immune checkpoint inhibitors like Nivolumab. ABVD, which stands for Adriamycin, Bleomycin, Vinblastine, and Dacarbazine, works by damaging the DNA of cancer cells, thereby preventing them from dividing and growing. Nivolumab, on the other hand, is a PD-1 inhibitor that blocks the programmed cell death protein 1 (PD-1) pathway, which cancer cells often exploit to evade the immune system. By inhibiting this pathway, Nivolumab helps the immune system recognize and attack cancer cells more effectively. These treatments are crucial for Hodgkin's Lymphoma patients as they target the cancer cells directly and enhance the body's immune response, thereby improving the chances of remission and cure.