A Study of Safety and Efficacy of Nivolumab and Bendamustine (NB) in Patients With Relapsed/Refractory Hodgkin's Lymphoma

Study Overview
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Brief Summary
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A clinical study of safety and efficacy of treatment with Nivolumab and Bendamustine (NB) in patients with relapsed/refractory Hodgkin's lymphoma.

Official Title
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A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of Nivolumab and Bendamustine Combination (NB) in Patients With Relapsed or Refractory Hodgkin's Lymphoma

Conditions
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Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Bendamustine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis: Histologically confirmed Hodgkin's lymphoma Relapsed or refractory to at least two prior treatment lines Relapsed after nivolumab treatment or refractory to nivolumab treatment Age 18-70 years old 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 Karnofsky index <30% Pregnancy Somatic or psychiatric disorder making the patient unable to sign 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: NB<br>Nivolumab 3 mg/kg IV infusion on day 1,14 + Bendamustine hydrochloride 90 mg/kg IV infusion on day 1,2 up to 3 cycles. Duration of cycle 28 days | Drug: Nivolumab<br>* 3 mg/kg IV infusion on day 1,14 up to 3 cycles<br>* Other names: Opdivo;Drug: Bendamustine Hydrochloride<br>* 90 mg/kg IV infusion on day 1 up to 3 cycles<br>* Other names: Ribomustin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) of Nivolumab in combination with Bendamustine Hydrochloride in patients with Hodgkin's lymphoma | Overall response rate (ORR), defined as proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by LYRIC criteria and duration of response. | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03 | Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment). | up to 12 months | 
| Duration of Response (DOR) | Duration of response will be measured from the time of initial response to nivolumab till documented disease progression, death or last evaluation of tumor status. | up to 12 months | 
| Time to Progression (TTP) |  | up to 12 months | 
| Progression-Free Survival (PFS) |  | up to 12 months | 
| Overall Survival (OS) |  | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's Lymphoma, Nivolumab, Bendamustine Hydrochloride