Clinical trial NCT03580408: Study Of Nivolumab Alone, Or In Combination With Vinblastin In Patients With Classical Hodgkin Lymphoma
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Coexisting Medical Conditions
Keywords: Nivolumab
Lymphoma
Anti-PD1
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2018-07-09
Enrollment: 64
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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) :

  1. Calculated creatinine clearance \< 30 mL/min (MDRD formula)
  2. aspartate transaminase (AST) or alanine transaminase (ALT) \> 2.5 times the upper limit of normal (ULN)
  3. Serum total bilirubin \> 30µmol/L
  4. Neutrophils\<1 G/L or Platelets\<50 G/L, (unless related to bone infiltration by lymphoma)
* 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 :

  1. 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,
  2. They had definitive curative therapy (ie, prostatectomy or radiotherapy) ≥ 2 years before Day 1 of Cycle 1,
  3. 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.
* Uncontrolled diabetes mellitus leading to impossibility to perform PET scan
* Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
* Adult person under legal protection
* Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
* Subjects with know Human Immunodeficiency Virus (HIV) positivity
* 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)
* 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.

Primary outcomes:
measure: Complete Metabolic Response (CMR) rate (Deauville scale 1-3) at the end of treatment
timeFrame: 12 months
Secondary outcomes:
measure: Quantity of drug taken
timeFrame: 12 months
measure: Number of Serious Adverse Event
timeFrame: 12 months
measure: Progression-free survival (PFS)
timeFrame: 5 years
measure: Event-free survival (EFS)
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Complete Metabolic Response (CMR) rate
timeFrame: 3 months
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Bruges
country: Belgium
facility: Az Sint Jan
city: Brussels
country: Belgium
facility: Clinique Universitaire Saint LUC
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Haine saint paul
country: Belgium
facility: Hopital Jolimont
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Liege
country: Belgium
facility: CHU de Liege
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne
city: Yvoir
country: Belgium
facility: CHU UCL Namur
city: Amiens
country: France
facility: CHU d'Amiens
city: Avignon
country: France
facility: CH d'Avignon - Hôpital Henri Duffaut
city: Bayonne
country: France
facility: CH Côte Basque
city: Besançon
country: France
facility: CHU de Besançon - Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié - Bordeaux
city: Caen
country: France
facility: Institut d'Hématologie de Basse Normandie - CHU Côte de Nacre
city: Chambery
country: France
facility: CH Métropole Savoie
city: Clermont Ferrand
country: France
facility: CHU de Clermont Ferrand
city: Corbeil Essonnes
country: France
facility: CH Sud Francilien de Corbeil
city: Créteil
country: France
facility: APHP-Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon - Hôpital le Bocage
city: Grenoble
country: France
facility: CHU de Grenoble
city: La Roche-sur-Yon
country: France
facility: CHD de Vendée
city: La Rochelle
country: France
facility: CH La Rochelle
city: Le Mans
country: France
facility: CH du Mans
city: Lille
country: France
facility: CH Saint Vincent de Paul
city: Lille
country: France
facility: CHRU de LILLE - Claude Huriez
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon Cedex 8
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Metz
country: France
facility: CHRU de Metz-Thionville
city: Montpellier
country: France
facility: CHU de Montpellier - Saint Eloi
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nimes
country: France
facility: CHU de Nîmes - Caremeau
city: Paris Cedex 10
country: France
facility: APHP - Hôpital Saint Louis
city: Paris
country: France
facility: APHP - Hopital Necker
city: Paris
country: France
facility: APHP - Hôpital de la Pitié Salpetrière
city: Pessac
country: France
facility: Centre François Magendie - Hôpital du Haut Lévêque
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers - Hôpital de La Milétrie
city: Pontoise
country: France
facility: Ch Rene Dubos
city: Pringy
country: France
facility: Centre Hospitalier Annecy-Genevois - Site d'Annecy
city: Reims
country: France
facility: CHU Robert Debré
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Roubaix
country: France
facility: CH de Roubaix
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Brieuc
country: France
facility: CH de Saint Brieuc
city: Strasbourg
country: France
facility: CHRU de Strasbourg
city: Toulouse
country: France
facility: IUCT Toulouse
city: Tours
country: France
facility: CHU Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: CHU Brabois
city: VILLEJUIF Cedex
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut Gustave Roussy Cancer, Villejuif, France - LYSA
name: Vincent RIBRAG
role: STUDY_CHAIR
affiliation: Institut Gustave Roussy Cancer, Villejuif, France - LYSA
name: Julien LAZAROVICI
role: STUDY_CHAIR
affiliation: CHU Dinant Godinne, UCL Namur, Yvoir - Belgium - LYSA
name: Marc ANDRE
role: STUDY_CHAIR
References: