Improvement of Outcome in Elderly Patients or Patients not eligible forhigh-dose chemotherapy with Aggressive Non-Hodgkin Lymphoma infirst Relapse or Progression by adding Nivolumab to Gemcitabine,Oxaliplatin plus Rituximab in case of B-cell lymphoma.

Phase 1

• Conditions: on-Hodgkin's Lymphoma; MedDRA version: 22.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-002272-27-PL
• Lead Sponsor: Saarland University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-14
• Last Update Posted: 21 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 388

Inclusion Criteria

1. Age: all patient >65 years of age or > 18 years if not eligible for neither
autologous nor allogeneic stem cell transplantation
2. Ineligibility for neither autologous nor allogeneic stem cell transplantation as defined as:
>65 years of age or
older than 18 years if HCT-CI score > 2 (cf. Appendix 24.2) or patients who underwent prior autologous stem cell transplantation and are not eligible for allogeneic stem cell transplantation
3. Risk group: All risk groups (IPI 0 to 5)
4. Histology: 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.
5. Performance status: Performance status ECOG 0 – 2.
6. Previous therapy: Patients must have 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. Patients may have received prior radiation therapy as part of their first-line therapy.
7. Men who are sexually active with women of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year.
8. Written informed consent of the patient.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Already initiated lymphoma therapy after first relapse or progression (except for the prephase treatment, cf. 8.6.1).
2. Serious accompanying disorder or impaired organ function (except when due to lymphoma involvement)
3. WBC < 2.5 G/l, Neutrophils < 2 G/l, Platelets < 100 G/l (does not apply if cytopenia is caused by lymphoma)
4. 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.
5. Family history for Long QT-syndrome
6. Patients with an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have 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
7. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration (except for treatment of lymphoma).
8. Chronic active hepatitis B or C as defined either HBs Ag positive or HBc Ac positive with detectable viral DNA or hepatitis C virus ribonucleic acid positive.
9. HIV-infection
10. Patients with a severe immunodeficiency
11. Previous therapy with Nivolumab, Gemcitabine or Oxaliplatin.
12. Patients with a currently active” second malignancy other than non-melanoma skin cancer. Patients are not considered to have a currently active” malignancy if they have completed therapy since 6 months and are considered by their physician to be less than 30% risk of relapse within one year.
13. CNS involvement of lymphoma (intracerebral, meningeal, intraspinal intradural) or primary CNS lymphoma
14. Persistent neuropathy grade >2 (NCI CTC-AE v4.03) (unless due to lymphoma involvement)
15. Pregnancy or breast-feeding women
16. Women of childbearing potential (WOCBP). A WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level higher than 40 mIU/mL.
17. Active serious infections not controlled by oral and/or intravenous antibiotics or antifungal medication
18. Any medical condition which in the opinion of the investigator places the subject at an unacceptably high risk for toxicities
19. Lymphomas other than those listed in the inclusion criteria notably indolent lymphoma, Mantle cell lymphoma, Burkitt lymphoma, adult T-cell leukemia/lymphoma.
20. Persons not able to understand the impact, nature, risks and consequences of the trial (including language barrier)
21. Persons not agreeing to the transmission of their pseudonymous data
22. Persons depending on sponsor or investigator
23. Persons from highly protected groups
24. 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified