Study Of Nivolumab Alone, Or In Combination With Vinblastin In Patients With Classical Hodgkin Lymphoma
- Conditions
- Coexisting Medical ConditionsHodgkin Lymphoma
- Interventions
- Registration Number
- NCT03580408
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- 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.
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Contra-indication to Nivolumab and /or Vinblastin
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Subjects with active interstitial pneumonitis
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Subjects with active infectious disease
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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.
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Any serious active disease, severe cardio-pulmonary, or metabolic disease interfering with normal application of protocol treatment (according to the investigator's decision)
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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)
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Any history of cancer evolution requiring therapy during the last 3 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Patients previously diagnosed with prostate cancer are eligible if :
- Their disease was T1-T2a, N0, M0, with a Gleason score ≤ 7, and a prostate specific antigen (PSA) ≤ 10 ng/mL prior to initial therapy,
- They had definitive curative therapy (ie, prostatectomy or radiotherapy) ≥ 2 years before Day 1 of Cycle 1,
- At a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or <1 ng/mL if they did not undergo prostatectomy.
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Uncontrolled diabetes mellitus leading to impossibility to perform PET scan
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Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
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Adult person under legal protection
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Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
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Subjects with know Human Immunodeficiency Virus (HIV) positivity
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Subjects with known active hepatitis B (HB) infection (positive Ag HB s or positive DNA polymerase chain reaction (PCR) or positive antibody anti-HB c with lack of antibody against HBs) or active hepatitis C infection (patients with positive HCV serology are eligible only if PCR is negative for known hepatitis C virus (HCV RNA)
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Subjects with a condition requiring systemic treatment with either corticosteroids (> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Vinblastin 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. Experimental Nivolumab 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.
- Primary Outcome Measures
Name Time Method Complete Metabolic Response (CMR) rate (Deauville scale 1-3) at the end of treatment 12 months by the Lugano classification 2014
- Secondary Outcome Measures
Name Time Method 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 by the Lugano classification 2014 at the end of induction treatment
Trial Locations
- Locations (51)
CHU de Clermont Ferrand
🇫🇷Clermont Ferrand, France
CHU de Dijon - Hôpital le Bocage
🇫🇷Dijon, France
Clinique Universitaire Saint LUC
🇧🇪Brussels, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
CH La Rochelle
🇫🇷La Rochelle, France
CH Métropole Savoie
🇫🇷Chambery, France
APHP-Hôpital Henri Mondor
🇫🇷Créteil, France
CH Saint Vincent de Paul
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon Cedex 8, France
CHU Brabois
🇫🇷Vandoeuvre les Nancy, France
CHD de Vendée
🇫🇷La Roche-sur-Yon, France
CH du Mans
🇫🇷Le Mans, France
CHU d'Amiens
🇫🇷Amiens, France
Hopital Jolimont
🇧🇪Haine saint paul, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Az Sint Jan
🇧🇪Bruges, Belgium
CHU UCL Namur
🇧🇪Yvoir, Belgium
CH Côte Basque
🇫🇷Bayonne, France
CHU de Rennes - Hôpital Pontchaillou
🇫🇷Rennes, France
Centre Henri Becquerel
🇫🇷Rouen, France
CH de Saint Brieuc
🇫🇷Saint-Brieuc, France
Institut Gustave Roussy
🇫🇷VILLEJUIF Cedex, France
IUCT Toulouse
🇫🇷Toulouse, France
APHP - Hôpital de la Pitié Salpetrière
🇫🇷Paris, France
CHU Bretonneau
🇫🇷Tours, France
CHU de Montpellier - Saint Eloi
🇫🇷Montpellier, France
CHU de Nîmes - Caremeau
🇫🇷Nimes, France
CHU Robert Debré
🇫🇷Reims, France
CH de Roubaix
🇫🇷Roubaix, France
CHU de Poitiers - Hôpital de La Milétrie
🇫🇷Poitiers, France
Ch Rene Dubos
🇫🇷Pontoise, France
CHRU de Strasbourg
🇫🇷Strasbourg, France
CHU de Limoges
🇫🇷Limoges, France
Az Groeninge
🇧🇪Kortrijk, Belgium
CHU de Liege
🇧🇪Liege, Belgium
CHU Dinant Godinne
🇧🇪Yvoir, Belgium
CH d'Avignon - Hôpital Henri Duffaut
🇫🇷Avignon, France
Institut d'Hématologie de Basse Normandie - CHU Côte de Nacre
🇫🇷Caen, France
CH Sud Francilien de Corbeil
🇫🇷Corbeil Essonnes, France
CHU de Besançon - Hôpital Jean Minjoz
🇫🇷Besançon, France
Institut Bergonié - Bordeaux
🇫🇷Bordeaux, France
CHU de Grenoble
🇫🇷Grenoble, France
CHRU de LILLE - Claude Huriez
🇫🇷Lille, France
APHP - Hôpital Saint Louis
🇫🇷Paris Cedex 10, France
Institut Paoli Calmette
🇫🇷Marseille, France
CHRU de Metz-Thionville
🇫🇷Metz, France
CHU de Nantes - Hôtel Dieu
🇫🇷Nantes, France
Centre François Magendie - Hôpital du Haut Lévêque
🇫🇷Pessac, France
CHU Lyon Sud
🇫🇷Pierre-Bénite, France
Centre Hospitalier Annecy-Genevois - Site d'Annecy
🇫🇷Pringy, France
APHP - Hopital Necker
🇫🇷Paris, France