Multicenter Study of Safety and Efficacy of PET-adapted Treatment With Nivolumab, Bendamustine, Gemcitabine, Vinorelbine (Nivo-BeGEV) in Patients With Relapsed/Refractory Hodgkin Lymphoma

Study Overview
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Brief Summary
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Nivolumab is an anti-PD-1 antibody highly effective in patients with relapsed/refractory classical Hodgkin lymphoma. A PET-adapted regimen of nivolumab combined with salvage therapy was shown to induce high response rates and favorable progression-free survival as a bridge to autologous stem cell transplantation, allowing to omit salvage chemotherapy in a substantial proportion of r\r cHL patients. This study evaluates the safety and efficacy of PET-adapted treatment of nivolumab at the 3 mg/kg in combination with Bendamustine, Gemcitabine, Vinorelbine (Nivo-BeGEV) in patients with relapsed/refractory Hodgkin Lymphoma.

Official Title
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Multicenter Study of Safety and Efficacy of PET-adapted Treatment With Nivolumab, Bendamustine, Gemcitabine, Vinorelbine (Nivo-BeGEV) in Patients With Relapsed/Refractory Hodgkin Lymphoma

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis: Histologically confirmed Hodgkins lymphoma Relapsed or refractory disease after the first line of treatment Age 18-70 years old Ejection fraction greater than 50% ECOG 0-2 status Signed informed consent No severe concurrent illness Exclusion Criteria: Uncontrolled bacterial or fungal infection at the time of enrollment Requirement for vasopressor support at the time of enrollment Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 norms Karnofsky index <30% Pregnancy Somatic or psychiatric disorder making the patient unable to sign an informed consent Active or prior documented autoimmune disease requiring systemic treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main arm<br>Patients will receive for a maximum of 4 cycles of nivolumab 3 mg/kg on day 0 BeGEV , with subsequent assessment of response by PET-CT. Patients with CR after 2 cycles Nivo-BeGEV will proceed to ASCT. Patients with <CR after 2 cycles of a combination Nivo-BeGEV, with subsequent PET-CT assessment, will receive an additional 2 cycles Nivo-BeGEV. Patients with CR after 4 cycles Nivo-BeGEV will proceed to ASCT. | Drug: Nivolumab<br>* Drug: Nivolumab Schedule: Nivolumab 3 mg/kg on day 0 of the Nivo-BeGEV or a maximum of 4 cycles Drug: Bendamustine Schedule: Day 2: Bendamustine 90mg/mq Day 3: Bendamustine 90mg/mq for a maximum of 4 cycles Other Name: Ribomustin Drug: Gemcitabine Day 1: Gemcitabine 800mg/mq, Day 4: Gemcitabine 800mg/mq for a maximum of 4 cycles Other Name: Gemzar Drug: Vinorelbine Day 1 Vinorelbine 20mg/mq for a maximum of 4 cycles Other Name: Navelbine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03 Toxicity parameters based on NCI CTCAE 4.03 grades |  | 12 months | 
| 2. Overall Response Rate (ORR) Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by LYRIC and Lugano 2014 criteria |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Duration of Response (DOR) |  | 24 months | 
| Overall Survival (OS) |  | 24 months | 
| Progression-Free Survival (PFS) |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET-adapted Treatment, Relapsed/Refractory Hodgkin Lymphoma, Nivolumab, BeGEV