Patients with Relapsed-Refractory Diffuse Large B-cell Lymphoma MedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: ALIQOPA
Product Name: ALIQOPA
Product Code: [BAY 80-6946]
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Copanlisib
CAS Number: 1032568-63-0
Current Spon
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of DLBCL (de-novo DLBCL or DLBCL transformed by indolent lymphoma; high grade double hit lymphoma can be included); new biopsy at relapse time is recommended, but not mandatory. 2. Patients must have relapsed (recurrence after complete response or presented progression after partial response) or refractory after at least = 1 (but =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Primary mediastinal B-cell Lymphoma (PMBCL) 2. High grade B-lymphoma NOS (other morphology) 3. Known lymphomatous involvement of the central nervous system 4. Congestive heart failure > New York Heart Association (NYHA) class 2 5. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). 6. Myocardial infarction less than 6 months before start of test drug 7. Uncontrolled arterial hypertension despite optimal medical management 8. HbA1c> 8.5% 9. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication 10. Non-healing wound, ulcer, or bone fracture 11. Active, clinically serious infections > CTCAE Grade 2 12. History of, or current autoimmune disease 13. Known history of Human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations. 14. Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA 15. CMV PCR positive at baseline 16. Previous or concurrent history of malignancies other than DLBCL within 5 years prior to study treatment except for curatively treated: • Cervical carcinoma in situ • Non-melanoma skin cancer • Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) • Localized prostate cancer 17. Patients with seizure disorder requiring medication 18. Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study medication 19. Proteinuria of = CTCAE Grade 3 as assessed by a 24h protein quantification or estimated by urine protein: creatinine ratio > 3.5 on a random urine sample 20. History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) 21. Concurrent diagnosis of pheochromocytoma 22. Pregnant or breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment. 23. Unresolved toxicity higher than CTCAE Grade 1 attributed to any prior therapy/procedure, excluding alopecia 24. Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation 25. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results 26. Any illness or medical conditions that are unstable or could jeopardize the safety of patients and their compliance in the study e.g., uncontrolled diabetes, uncontrolled dyslipidemia, etc.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1- To explore the improvement of PFS by adding copanlisib to rituximab-bendamustine combination (copa-RB) in Relapsed/Refractory Diffuse Large B-cell Lymphoma;Secondary Objective: 1 - To evaluate the copa-RB schedule by assessing: -its efficacy in terms of overall survival (OS); -its activity in terms of overall response rate (ORR); -its activity in terms of complete response rate (CRR); -its efficacy in terms of duration of response (DOR); -its activity in terms of conversion rate from SD/PR to PR/CR with copanlisib maintenance. 2 - To evaluate the safety of the copa-RB combination. 3 - To evaluate health-related quality of life (HRQoL) as measured by the EuroQol 5-Dimension Scale (EQ-5D-5L) and the Functional Assessment of Cancer Therapy for Patients with Lymphoma (FACT–Lym) standardized questionnaire on health status.;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Time between the date of enrolment and the date of disease progression, relapse or death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS); Overall Response Rate (ORR); Duration of response (DOR); Complete Response Rate (CRR); Conversion rate from SD/PR to PR/CR with maintenance; Evaluation of adverse events according to the current version of the CTCAE criteria;Timepoint(s) of evaluation of this end point: Time between the date of enrolment and the date of death from any cause. Patients who have not died at the time of the final analysis will be censored at the date of the last contact.; End of treament (EOT), 30 months; Time from the date when criteria for response are met (CR or PR) until the date of progression or relapse. Patients without relapse or progression or death from other causes will be censored at their last assessment date.; End of induction (EOI), 18 months; End of treatment (after maintenance), 30 months; Throughout the duration of the study | — |
Countries
Italy, United States
Contacts
Public ContactUffici Studi FIL - Area Start up
FONDAZIONE ITALIANA LINFOMI ONLUS
Outcome results
None listed