Study Of Nivolumab Alone, Or In Combination With Vinblastin In Patients With Classical Hodgkin Lymphoma

Hodgkin Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03580408
• Other study ID #: NIVINIHO
• Status: Completed
• Phase: Phase 2
• Start date: August 31, 2018
• Est. completion date: August 12, 2021

Study information

• Verified date: August 2022
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 12, 2021
• Est. primary completion date: February 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 61 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coexisting Medical Conditions
• Disease
• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Nivolumab
240 mg
• Vinblastin
6mg/m²

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	Az Sint Jan	Bruges
Belgium	Clinique Universitaire Saint LUC	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Hopital Jolimont	Haine saint paul
Belgium	Az Groeninge	Kortrijk
Belgium	CHU de Liege	Liege
Belgium	CHU Dinant Godinne	Yvoir
Belgium	CHU UCL Namur	Yvoir
France	CHU d'Amiens	Amiens
France	CH d'Avignon - Hôpital Henri Duffaut	Avignon
France	CH Côte Basque	Bayonne
France	CHU de Besançon - Hôpital Jean Minjoz	Besançon
France	Institut Bergonié - Bordeaux	Bordeaux
France	Institut d'Hématologie de Basse Normandie - CHU Côte de Nacre	Caen
France	CH Métropole Savoie	Chambery
France	CHU de Clermont Ferrand	Clermont Ferrand
France	CH Sud Francilien de Corbeil	Corbeil Essonnes
France	APHP-Hôpital Henri Mondor	Créteil
France	CHU de Dijon - Hôpital le Bocage	Dijon
France	CHU de Grenoble	Grenoble
France	CHD de Vendée	La Roche-sur-Yon
France	CH La Rochelle	La Rochelle
France	CH du Mans	Le Mans
France	CH Saint Vincent de Paul	Lille
France	CHRU de LILLE - Claude Huriez	Lille
France	CHU de Limoges	Limoges
France	Centre Leon Berard	Lyon Cedex 8
France	Institut Paoli Calmette	Marseille
France	CHRU de Metz-Thionville	Metz
France	CHU de Montpellier - Saint Eloi	Montpellier
France	CHU de Nantes - Hôtel Dieu	Nantes
France	CHU de Nîmes - Caremeau	Nimes
France	APHP - Hôpital de la Pitié Salpetrière	Paris
France	APHP - Hopital Necker	Paris
France	APHP - Hôpital Saint Louis	Paris Cedex 10
France	Centre François Magendie - Hôpital du Haut Lévêque	Pessac
France	CHU Lyon Sud	Pierre-Bénite
France	CHU de Poitiers - Hôpital de La Milétrie	Poitiers
France	Ch Rene Dubos	Pontoise
France	Centre Hospitalier Annecy-Genevois - Site d'Annecy	Pringy
France	CHU Robert Debré	Reims
France	CHU de Rennes - Hôpital Pontchaillou	Rennes
France	CH de Roubaix	Roubaix
France	Centre Henri Becquerel	Rouen
France	CH de Saint Brieuc	Saint-Brieuc
France	CHRU de Strasbourg	Strasbourg
France	IUCT Toulouse	Toulouse
France	CHU Bretonneau	Tours
France	CHU Brabois	Vandoeuvre les Nancy
France	Institut Gustave Roussy	VILLEJUIF Cedex

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Metabolic Response (CMR) rate (Deauville scale 1-3) at the end of treatment	by the Lugano classification 2014	12 months
Secondary	Quantity of drug taken		12 months
Secondary	Number of Serious Adverse Event		12 months
Secondary	Progression-free survival (PFS)		5 years
Secondary	Event-free survival (EFS)		5 years
Secondary	Overall survival (OS)		5 years
Secondary	Complete Metabolic Response (CMR) rate	by the Lugano classification 2014 at the end of induction treatment	3 months