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Trial record 1 of 1 for:    NCT03366272
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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

Brief Summary:
This study evaluates the addition of nivolumab to gemcitabine, oxaliplatin plus rituximab in case of B-cell lymphoma

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Drug: Nivolumab Drug: Rituximab Drug: Gemcitabine Device: Oxaliplatin Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 388 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 5, 2017
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
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)
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

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
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




Primary Outcome Measures :
  1. PFS [ Time Frame: 1 year ]
    Progression free survival


Secondary Outcome Measures :
  1. CR rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
    complete response rate

  2. PR rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
    partial response rate

  3. ORR rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
    overall response rate

  4. Duration of response [ Time Frame: up to 2 years after inclusion of last patient ]
    Duration of response

  5. Primary Progression rate [ Time Frame: up to 2 years after inclusion of last patient ]
    Rate of Primary progression

  6. Treatment related deaths rate [ Time Frame: up to 2 years after inclusion of last patient ]
    Rate of Treatment related deaths

  7. Relapse rate [ Time Frame: up to 2 years after inclusion of last patient ]
    Rate of relapses

  8. EFS [ Time Frame: up to 2 years after inclusion of last patient ]
    Event free survival

  9. OS [ Time Frame: up to 2 years after inclusion of last patient ]
    Overall survival

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366272


Contacts
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Contact: Viola Poeschel, MD +49- 6841-16 ext 15017 viola.poschel@uks.eu

Locations
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Sponsors and Collaborators
Universität des Saarlandes
Bristol-Myers Squibb
Lymphoma Study Association
University of Leipzig
Investigators
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Principal Investigator: Gerhard Held, Prof Universität des Saarlandes
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Responsible Party: Universität des Saarlandes
ClinicalTrials.gov Identifier: NCT03366272    
Other Study ID Numbers: DSHNHL 2015-1
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: December 1, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Rituximab
Nivolumab
Oxaliplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immune Checkpoint Inhibitors