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Nivolumab With Gemcitabine, Oxaliplatin + Rituximab in r/r Elderly Lymphoma Patients (NIVEAU)

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ClinicalTrials.gov Identifier: NCT03366272
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : December 1, 2021
Sponsor:
Collaborators:
Bristol-Myers Squibb
Lymphoma Study Association
University of Leipzig
Information provided by (Responsible Party):
Universität des Saarlandes

Tracking Information
First Submitted Date  ICMJE September 16, 2017
First Posted Date  ICMJE December 8, 2017
Last Update Posted Date December 1, 2021
Actual Study Start Date  ICMJE December 5, 2017
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
PFS [ Time Frame: 1 year ]
Progression free survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • CR rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
    complete response rate
  • PR rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
    partial response rate
  • ORR rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
    overall response rate
  • Duration of response [ Time Frame: up to 2 years after inclusion of last patient ]
    Duration of response
  • Primary Progression rate [ Time Frame: up to 2 years after inclusion of last patient ]
    Rate of Primary progression
  • Treatment related deaths rate [ Time Frame: up to 2 years after inclusion of last patient ]
    Rate of Treatment related deaths
  • Relapse rate [ Time Frame: up to 2 years after inclusion of last patient ]
    Rate of relapses
  • EFS [ Time Frame: up to 2 years after inclusion of last patient ]
    Event free survival
  • OS [ Time Frame: up to 2 years after inclusion of last patient ]
    Overall survival
  • Toxicities: rates and grades of adverse events [ Time Frame: up to 2 years after inclusion of last patient ]
    Toxicity: Rates and grades of toxicities will be determined according to CTC-v4.03
  • Protocol adherence according to number of given chemotherapy cycles [ Time Frame: up to 2 years after inclusion of last patient ]
    Protocol adherence will be determined according to number of chemotherapy cycles
  • Protocol adherence according to duration of given chemotherapy cycles [ Time Frame: up to 2 years after inclusion of last patient ]
    Protocol adherence will be determined according to duration of chemotherapy cycles
  • Protocol adherence according to cumulative dose of immunochemotherapy given [ Time Frame: up to 2 years after inclusion of last patient ]
    Protocol adherence will be determined according to cumulative dose of immunochemotherapy given
  • Protocol adherence according to relative dose of immunochemotherapy given [ Time Frame: up to 2 years after inclusion of last patient ]
    Protocol adherence will be determined according to relative dose of immunochemotherapy given
  • QoL [ Time Frame: up to 1 year after inclusion of last patient ]
    Quality of Life (QoL) will be assessed by the EQ-5D-5L questionnaire
  • Biological Parameters according to PD-L1 expression alterations [ Time Frame: up to 2 years after inclusion of last patient ]
    Outcome assessment of response according to PD-L1 expression alterations
  • Biological Parameters according to PD-1 expression [ Time Frame: up to 2 years after inclusion of last patient ]
    Outcome assessment of response according to PD-1 expression
  • Biological Parameters according to cell of origin [ Time Frame: up to 2 years after inclusion of last patient ]
    Outcome assessment of response according to cell of origin
  • Biological Parameters according to 9p24.1 alterations [ Time Frame: up to 2 years after inclusion of last patient ]
    Outcome assessment of response according to 9p24.1 alterations
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab With Gemcitabine, Oxaliplatin + Rituximab in r/r Elderly Lymphoma Patients
Official Title  ICMJE Improvement of Outcome in Elderly Patients or Patients Not Eligible for High-dose Chemotherapy With Aggressive NHL in First Relapse/Progression by Adding Nivolumab to Gemcitabine, Oxaliplatin Plus Rituximab in Case of B-cell Lymphoma
Brief Summary This study evaluates the addition of nivolumab to gemcitabine, oxaliplatin plus rituximab in case of B-cell lymphoma
Detailed Description International, multicentre, randomised, open-label, treatment optimisation study, preceded by safety run-in phases conducted for B-cell and T-cell lymphoma separately.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Non-Hodgkin
Intervention  ICMJE
  • Drug: Nivolumab
    eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
  • Drug: Rituximab
    eight cycles of R-GemOx in 2-wk intervals
  • Drug: Gemcitabine
    eight cycles of (R)-GemOx in 2-wk intervals
  • Device: Oxaliplatin
    eight cycles of (R)-GemOx in 2-wk intervals
Study Arms  ICMJE
  • Active Comparator: (R)-GemOx
    eight cycles of (R)-GemOx (Gemcitabine 1000 mg/m2, d1, Oxaliplatin 100 mg/m2, d1, Rituximab 375 mg/m2 in case of B-cell lymphoma disease, repeated every 2 wks)
    Interventions:
    • Drug: Rituximab
    • Drug: Gemcitabine
    • Device: Oxaliplatin
  • Experimental: Nivo-(R)-GemOx
    eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
    Interventions:
    • Drug: Nivolumab
    • Drug: Rituximab
    • Drug: Gemcitabine
    • Device: Oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2017)
388
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2024
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • patients with first relapse or progression of an aggressive Non-Hodgkin's lymphoma
  • all patient >65 years of age or > 18 years if not eligible for neither autologous nor allogeneic stem cell transplantation
  • all patient >65 years of age or older than 18 years if HCT-CI score > 2 or patients who underwent prior autologous stem cell transplantation and are not eligible for allogeneic stem cell Transplantation
  • All risk groups (IPI 0 to 5)
  • Diagnosis of aggressive Non-Hodgkin's lymphoma, based on an excisional biopsy of a lymph node or on an appropriate sample of a lymph node or of an extranodal involvement at initial diagnosis or relapse or Progression. The entities treated in the study will be based on the WHO 2017 classification.
  • ECOG 0 - 2
  • only one prior chemotherapy regimen including an anthracycline. The last cytotoxic drug must be given at least four weeks before entering the study. Rituximab must be part of the first-line regimen in case of B-cell lymphoma (except for primary CD20- negative lymphoma). Patients may have received prior radiation therapy as part of their first-line therapy
  • Men who are sexually active with women of childbearing potential (WOCBP) must not father a child during and up to 6 months after GemOx and up to 12 months after Rituximab and/or Nivolumab. They are advised to do cryoconservation of sperm prior to treatment.
  • Written informed consent of the patient
  • Patient must be covered by social security system

Exclusion Criteria:

  • Already initiated lymphoma therapy after first relapse or progression
  • Serious accompanying disorder or impaired organ function
  • WBC < 2.5 G/l, Neutrophils < 2 G/l, Platelets < 100 G/l
  • Prolongation of QTc interval > 450 ms, demonstrated in one electrocardiogram (done as triplicate). This does not apply for patients with a block of the right and/or left bundle branch.
  • Family history for Long QT-Syndrome
  • active, known or suspected autoimmune disease
  • no requirement for immunosuppressive doses of systemic corticosteroids
  • Chronic active hepatitis B or C
  • HIV-infection
  • Patients with a severe immunodeficiency
  • Previous therapy with Nivolumab,Gemcitabine or Oxaliplatin
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancer
  • CNS involvement of lymphoma
  • Persistent neuropathy grade >2
  • Pregnancy or breast-feeding women
  • Women of childbearing potential
  • Active serious infections not controlled by oral and/or intravenous antibiotics or anti-fungal medication
  • Any medical condition which in the opinion of the investigator places the subject at an unacceptably high risk for toxicities
  • Lymphomas other than those listed in the inclusion criteria notably indolent lymphoma, Mantle cell lymphoma, Burkitt lymphoma, adult T-cell leukemia/lymphoma.
  • Persons not able to understand the impact, nature, risks and consequences of the trial (including language barrier)
  • Persons not agreeing to the transmission of their pseudonymous data
  • Persons depending on sponsor or investigator
  • Persons from highly protected Groups
  • Allergies and Adverse Drug Reaction History to study drug components
  • Participation in another clinical trial with drug intervention within 4 weeks prior to start of the first cycle and during the study. However, participation in a clinical trial of firstline therapy of lymphoma is allowed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Viola Poeschel, MD +49- 6841-16 ext 15017 viola.poschel@uks.eu
Listed Location Countries  ICMJE Austria,   Belgium,   France,   Germany,   Israel,   Netherlands,   Poland,   Portugal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03366272
Other Study ID Numbers  ICMJE DSHNHL 2015-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Universität des Saarlandes
Original Responsible Party University Hospital, Saarland
Current Study Sponsor  ICMJE Universität des Saarlandes
Original Study Sponsor  ICMJE University Hospital, Saarland
Collaborators  ICMJE
  • Bristol-Myers Squibb
  • Lymphoma Study Association
  • University of Leipzig
Investigators  ICMJE
Principal Investigator: Gerhard Held, Prof Universität des Saarlandes
PRS Account Universität des Saarlandes
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP