A Prospective Phase II Study Of Nivolumab Alone, Or In Combination With Vinblastin In Patients Aged 61 Years And Older, With Classical Hodgkin Lymphoma And Coexisting Medical Conditions.
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Hodgkin Lymphoma
- Sponsor
- The Lymphoma Academic Research Organisation
- Enrollment
- 64
- Locations
- 51
- Primary Endpoint
- Complete Metabolic Response (CMR) rate (Deauville scale 1-3) at the end of treatment
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study is a multicentric phase II open-label trial consisting of 6 cycles Nivolumab (2 weeks interval) followed by a PET-CT scan. The treatment will be allocated according to PET and CT scan responses. :
- In case of CMR according to Lugano Classification (Cheson et al.2014, PET-CT based response), patients will receive 18 additional cycles of Nivolumab, according to CT-based response at Cycle 12.
- In case of Partial Metabolic Response (PMR) or No Metabolic Response(NMR), according to Lugano Classification (Cheson et al.2014, PET-CT based response) patients will receive 12 to 18 cycles of Nivolumab combined with Vinblastin according to CT-based response at Cycle 12.
- In case of progressive disease, according to Lugano Classification (Cheson et al.2014, PET-CT scan based response) patients will be considered in treatment failure.
Investigators
Eligibility Criteria
Inclusion Criteria
- •first diagnosis of classical Hodgkin lymphoma according to World Health Organization (WHO) criteria excluding nodular lymphocyte predominant subtype
- •Age 61 years or older
- •Unfit for poly chemotherapy because of co-morbidities evaluated by a Cumulative Illness Rating Scale (CIRS) score ≥6)
- •No previous treatment for Hodgkin lymphoma
- •Ann Arbor stages: I-IV
- •Baseline 18-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT (PET0) performed before any treatment with at least one hypermetabolic lesion
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- •minimum life expectancy of 3 months
- •covered by a social security system
- •Men who are sexually active with women with childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug and for at least 7 months after the last drug administration.
Exclusion Criteria
- •Contra-indication to Nivolumab and /or Vinblastin
- •Subjects with active interstitial pneumonitis
- •Subjects with active infectious disease
- •Subjects with active, known or suspected autoimmune disease. Are permitted to enroll: subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- •Any serious active disease, severe cardio-pulmonary, or metabolic disease interfering with normal application of protocol treatment (according to the investigator's decision)
- •Any of the following abnormal laboratory values (unless due to underlying HL) :
- •Calculated creatinine clearance \< 30 mL/min (MDRD formula)
- •aspartate transaminase (AST) or alanine transaminase (ALT) \> 2.5 times the upper limit of normal (ULN)
- •Serum total bilirubin \> 30µmol/L
- •Neutrophils\<1 G/L or Platelets\<50 G/L, (unless related to bone infiltration by lymphoma)
Arms & Interventions
Experimental
Induction treatment :Nivolumab will be given alone at 240 mg flat dose every 2 weeks (i.e. one cycle) Patients will be assessed after 3 months of therapy (after 6 injections of Nivolumab) Consolidation treatment: It depends on the induction evaluation by PET-CT and CT-scan (Lugano 2014 criteria) : * For patients achieving CMR according to Lugano Classification : treatment by nivolumab 240 mg every 2 weeks for 9 months. * Patients who reach PMR and NMR after 3 months (according to Lugano Classification) will be treated by the Nivolumab+Vinblastin regimen every 2 weeks for 9 additional months: Vinblastin(6 mg/m2 (IV) + Nivolumab 240 mg (IV) * In case of progressive disease , patients will be considered in treatment failure.
Intervention: Nivolumab
Experimental
Induction treatment :Nivolumab will be given alone at 240 mg flat dose every 2 weeks (i.e. one cycle) Patients will be assessed after 3 months of therapy (after 6 injections of Nivolumab) Consolidation treatment: It depends on the induction evaluation by PET-CT and CT-scan (Lugano 2014 criteria) : * For patients achieving CMR according to Lugano Classification : treatment by nivolumab 240 mg every 2 weeks for 9 months. * Patients who reach PMR and NMR after 3 months (according to Lugano Classification) will be treated by the Nivolumab+Vinblastin regimen every 2 weeks for 9 additional months: Vinblastin(6 mg/m2 (IV) + Nivolumab 240 mg (IV) * In case of progressive disease , patients will be considered in treatment failure.
Intervention: Vinblastin
Outcomes
Primary Outcomes
Complete Metabolic Response (CMR) rate (Deauville scale 1-3) at the end of treatment
Time Frame: 12 months
by the Lugano classification 2014
Secondary Outcomes
- Quantity of drug taken(12 months)
- Number of Serious Adverse Event(12 months)
- Progression-free survival (PFS)(5 years)
- Event-free survival (EFS)(5 years)
- Overall survival (OS)(5 years)
- Complete Metabolic Response (CMR) rate(3 months)