diffuse large B-cell lymphoma MedDRA version: 18.1 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Imbruvica
Product Name: Ibrutinib
Product Code: PR-1
Pharmaceutical Form: Capsule
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Other descriptive name: IBRUTINIB
Concentration uni
Sponsors
GELTAMO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with confirmed histologically diagnosis of diffuse large B-cell lymphoma. 2. Subjects must be 18 years of age or older. 3. Non-germinal center B-cell-like (GCB) subtype according to Hans algorithm (local laboratories). A centralized evaluation by GEP will be carried out to confirm activated B-cell-like (ABC) subtype (commercial biotech lab to perform on paraphin samples), but a negative result will not exclude patient from the trial if a response is achieved after 4 cycles. 4. Relapsed or refractory disease after: at least 1 prior line of therapy that includes rituximab in combination with chemotherapy, or, after previous ASCT, or, after reduced intensity conditioning allogeneic transplant, unless patient is receiving immunosuppressive drugs or active graft versus host disease is present at study entry.(Refractory disease is defined as failing to achieve CR after the most recent treatment.) 5. Eastern Cooperative Oncology Group (ECOG) performance status ? 2. 6. Baseline FDG-PET scan demonstrating positive lesions (Deauville 4 or 5) compatible with CT defined anatomical tumor sites. 7. Hematology values must be within the following limits: a. absolute neutrophil count (ANC) ?1000/?L independent of growth factor support. b. platelets ?100000/?L or ?50000/?L if bone marrow involvement independent of transfusion support in either situation. 8. Biochemical values within the following limits: a. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ?2.5 x upper limit of normal (ULN). b. total bilirubin ?1.5 x ULN unless bilirubin rise is due to Gilbert?s syndrome or of non-hepatic origin. c. serum creatinine ?2 x ULN or estimated creatinine clearance (CCr) ?30 mL/min. 9. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug. 10. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [?-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. 11. Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing and able to participate in the study. 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 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: 1. Prior malignancy other than DLBCL, with the exception of adequately treated basal cell or squamous cell skin tumor, in situ cervical cancer, or other tumor from which the patient has been disease free for at least 2 years or which will not limit survival to < 2 years (Note: these cases must be discussed with the Principal Investigator). 2. Candidates to autologous stem cell transplant. 3. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib, or put the study outcomes at undue risk. 4. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. 5. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. 6. Treatment with any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 3 weeks before first dose of study drug (corticosteroids for disease-related symptoms allowed as indicated in section 2.7). 7. Prior treatment with ibrutinib or other BTK inhibitors. 8. Central nervous system (CNS) involvement by lymphoma. 9. History of stroke or intracranial hemorrhage within 6 months prior to randomization. 10. Requires anticoagulation with warfarin or equivalent Vitamin K antagonists. 11. Requires treatment with strong CYP3A inhibitors (see Section 2.7.1). 12. Grade ?2 toxicity (other than alopecia) related to prior anticancer therapy including radiation. 13. Known history of human immunodeficiency virus (HIV), active hepatitis C virus (HCV) (HCV; RNA polymerase chain reaction [PCR]-positive) or active Hepatitis B virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection requiring IV antibiotics. Subjects with PCR-negative HBV are permitted in the study. 14. Major surgery within 4 weeks before first dose of study drug. 15. Vaccinated with live, attenuated vaccines within 4 weeks of randomization. 16. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the efficacy of IR-GEMOX-Dexa combination as salvage regimen in patients with refractory/relapsed non-GCB diffuse large B cell lymphoma, in terms of overall response rate (ORR).;Secondary Objective: 1. To evaluate the efficacy of IR-GEMOX-Dexa combination followed by ibrutinib maintenance in terms of secondary endpoints (complete remision [CR], overall survival [OS], event free-survival [EFS], progression free survival [PFS] and response duration) 2. To determine the safety and tolerability of ibrutinib in combination with R GEMOX-Dexa 3. To determine the safety and tolerability of ibrutinib maintenance 4. Identify clinical and biological prognostic factors with influence on response rates and survival. 5. Correlate mutational status with response and survival. 6. To evaluate the relation of the PET/CT results with biological markers. 7. Correlate HLA polymorphisms with response and survival. 8. Correlate minimal residual disease (MRD) at the end of therapy (6-8 courses of IR-GEMOX) with PET/CT response and survival.;Primary end point(s): Overall response rate (complete remission + partial response) of ibrutinib in combination with rituximab, gemcitabine, oxaliplatin and dexamethasone;Timepoint(s) of evaluation of this end point: Timepoint of evaluation of this end point will be 2 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 CR rate during induction and maintenance phases. 2. Conversion rate from SD or PR to PR or CR during maintenance phase 3. Response duration. 4. Progression free survival 5. Event-free survival 6. Overall survival 7. Safety and tolerability of ibrutinib in combination rituximab, gemcitabine, oxaliplatin and dexamethasone 8. Safety and tolerability of ibrutinib maintenance 9. Influence of clinical and biological prognostic factors on response rates and survival. -Correlate mutational status with response and survival - Correlate HLA polymorphisms with response and survival -Correlate PET /CT response with biological markers 10.Correlate MRD at the end of therapy (6-8 courses of IR-GEMOX) with PET/CT response, PFS and OS.;Timepoint(s) of evaluation of this end point: Once the treatment is started, there will be a visits every 8 weeks until 2 years. A visit at day 30 after the end of the treatment. | — |
Countries
Spain
Contacts
Public ContactAngel Cedillo
SecretarIa Cientifica GELTAMO
Outcome results
None listed