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Lymphoma

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Hodgkin Lymphoma

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Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Immunoglobulins

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunoconjugates

Immunologic Factors

Immune Checkpoint Inhibitors

Immunotoxins

Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

Alex F. Herrera

Justin Kline, MD

Philippe Armand, MD, PhD

Philippe Armand

Tatyana Feldman, MD

Tatyana Feldman

Ian W Flinn, MD, PhD

Alex F Herrera

This phase II trial investigates how well brentuximab vedotin and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back after initial treatment (relapsed) or has not responded to initial treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Nivolumab is an antibody that enhances the immune system to better fight Hodgkin lymphoma cells. Giving brentuximab vedotin and nivolumab may be able to defer stem cell transplant treatment and spare the considerable cost and toxicity on transplantation.

PRIMARY OBJECTIVE:

I. Assess the durability of response to brentuximab vedotin (BV) plus nivolumab (nivo) by 24-month progression-free survival (PFS) in participants (with relapsed/refractory classical Hodgkin lymphoma (RcHL) after frontline therapy) who achieved early complete metabolic response (CMR) (CMR after 4 cycles).

SECONDARY OBJECTIVES:

I. Estimate CMR and overall response rate (ORR) after 4 cycles and at the end of BV-nivo therapy.

II. Estimate the PFS and overall survival (OS) for the entire cohort and for subgroups of patients defined by their response.

III. Estimate the PFS and OS separately for responders who did and did not receive radiotherapy.

IV. Evaluate the toxicities of BV-nivo in the study population.

EXPLORATORY OBJECTIVES:

I. Estimate the second PFS after salvage therapy for patients who progress after study therapy, and for the subset of these patients who proceeded to autologous stem cell transplant (ASCT).

II. Explore the association between clinical outcomes and pathological tumor characteristics.

III. Explore the association between clinical outcomes and circulating tumor deoxyribonucleic acid (ctDNA) characteristics (mutation profile, kinetics of clearance).

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and 6, 12, 18, 24, 36, 48, and 60 months.

Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

A Phase 2 Study of Brentuximab Vedotin Plus Nivolumab Without Stem Cell Consolidation in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Estimated using Kaplan-Meier product limit method.

Defined as the proportion of response-evaluable participants that achieve a best response of CMR with brentuximab vedotin (BV)-nivolumab (Nivo) therapy. Will be estimated along with the 95% exact binomial confidence interval.

defined as the proportion of response-evaluable participants that achieve a best response of either CMR or partial metabolic remission (PMR) with BV-Nivo therapy. Will be estimated along with the 95% exact binomial confidence interval.

Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation. Median PFS/OS will be estimated when available. PFS and OS will be estimated for the entire cohort, for subgroups defined by response, and for responders who did and did not receive radiotherapy.

Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Observed toxicities of BV-Nivo therapy will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity, and attribution.

National Cancer Institute (NCI)

City of Hope Medical Center

Azacitidine

Antimetabolites

Enzyme Inhibitors

Patients were treated by Azacitidine plus PD-1 therapy

Patients were treated by Azacytidine(75 mg/m2 subcutaneous injection qd on days 1-7) plus PD-1 therapy(200mg iv qd d8)

Azacitidine Plus PD-1 therapy

Liren Qian, PhD

Liren Qian, M.D.

The goal of this phase 2 trial is to test the safety and efficacy of azacitidine when given together with PD-1 therapy in treating patients with relapsed/refractory classic Hodgkin lymphoma.

The investigators will evaluate response rate, progression free survival (PFS), overall survival (OS), and toxicity of azacytidine combined with PD-1 therapy in classic relapsed/refractory Hodgkin lymphoma.

Azacitidine Plus PD-1 Therapy for R/R Hodgkin Lymphoma

Azacitidine Plus PD-1 Therapy for Relapsed/Refractory Hodgkin Lymphoma

ORR was defined as the proportion of patients who achieved CR or PR as their best response

OS was defined as time from diagnosis to death from any cause or the last follow-up

PFS using local assessment of progressive disease according to Lugano Response Criteria (2014)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed/Refractory Classical Hodgkin Lymphoma	NCT04561206	Relapsed Classi...	Brentuximab Ved... Nivolumab	18 Years -	City of Hope Medical Center
Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed/Refractory Classical Hodgkin Lymphoma	NCT04561206	Relapsed Classi...	Brentuximab Ved... Nivolumab	18 Years -	City of Hope Medical Center
Azacitidine Plus PD-1 Therapy for R/R Hodgkin Lymphoma	NCT06190067	Relapsed Classi... Refractory Clas...	Azacitidine Plu...	18 Years -	Navy General Hospital, Beijing
Azacitidine Plus PD-1 Therapy for R/R Hodgkin Lymphoma	NCT06190067	Relapsed Classi... Refractory Clas...	Azacitidine Plu...	18 Years -	Navy General Hospital, Beijing
Azacitidine Plus PD-1 Therapy for R/R Hodgkin Lymphoma	NCT06190067	Relapsed Classi... Refractory Clas...	Azacitidine Plu...	18 Years -	Navy General Hospital, Beijing

Spots Global Cancer Trial Database for relapsed classic hodgkin lymphoma