Young patients with DLBCL who failed or relapsed after one previous chemotherapy regimen. MedDRA version: 17.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Product Name: RO5072759
Product Code: GA101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OBINUTUZUMAB
CAS Number: 949142-50-1
Current Sponsor code: GA101DHAP
Other d
Sponsors
Fondazione Italiana Linfomi ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18= Age 1.5 x 109/L, Hgb > 10.5 g/dl (transfusion independent), Platelet count > 75 x 109/L (transfusion independent), with the exception of cytopenia due to lymphoma bone marrow involvement 9. Normal liver function (ALP, AST, ALT, GGT, conjugated bilirubin total 45 ml/min) 11. Cardiac ejection fraction > 50% (MUGA scan or echocardiography) 12. Normal lung function 13. Absence of active infections 14. Non peripheral neuropathy or active neurological non neoplastic disease of CNS 15. Non major surgical intervention prior 3 months to randomization if not due to lymphoma and/or not other disease life-threatening that can compromise chemotherapy treatment 16. Disease free of prior malignancies other than lymphoma for > 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast 17. Life expectancy > 6 months 18. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent 19. Written informed consent 20. Women must be: - postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months) - surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), - abstinent (at the discretion of the investigator/per local regulations), or - if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 12 months after terminating treatment. 21. Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening 22. Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug. 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 78 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma, Primary Mediastinal Lymphoma 2. Age = 65 years 3. Patients ineligible to high-dose chemotherapy 4. Performance status > 2 according to ECOG scale if not due to lymphoma 5. Patients who previously received GA101 (obinutuzumab) are excluded. 6. Patient has known or suspected hypersensitivity or intolerance to Rituximab 7. Patient has received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study. 8. CNS disease (meningeal and/or brain involvement by lymphoma) 9. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances 10. Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology) Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing. 11. Positive test results for hepatitis C (HCV antibody serology testing) Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. 12. Known history of HIV seropositive status For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations. 13. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug 14. Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis 15. Cardiac ejection fraction < 45% (MUGA scan or echocardiography) 16. Creatinine clearance < 45 ml/min 17. Presence of major neurological disorders 18. Active infection 19. Major surgical intervention prior 3 months to randomization if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment 20. Prior malignancies other than lymphoma in the last 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast 21. Life expectancy < 6 months 22. Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent. 23. If female, the patient is pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Overall Response Rate (ORR) prior to consolidation with BEAM and ASCT • Progression free survival (PFS) • Overall Survival (OS) • Feasibility and toxicity • The hematopoietic cell mobilization • The rate of patients actually proceeding to ASCT. ;Primary end point(s): The complete response rate (CR) evaluated by PET scan after four cycles of GA101-DHAP before ASCT according to Cheson criteria.;Timepoint(s) of evaluation of this end point: After 4 cycles of treatment with GA101-DHAP.;Main Objective: Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL. Primary objective is to assess whether the treatment achieves an absolute increase of the CR proportion of at least 20% (from 30% to 50%) with respect to the standard treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Overall response rate (ORR): a patient is defined as a responder if she/he has a complete or partial response, evaluated by PET/TC, after four cycles of GA101-DHAP 2- Progression free survival (PFS): measured from the date of starting salvage therapy to the date of disease progression, relapse or death from any cause. Responding patients and patients who are lost to follow up will be surveyed at their last assessment date. 3- OS: measured from the date of starting salvage therapy to the date of death from any cause. Patients alive at the time of the final analysis will be surveyed at the date of the last contact. For both PFS and OS minimum follow up time required for all patients will be 2 years. 4- Toxicity: severe, life-threatening, fatal (grade 3, 4 and 5) and/or serious adverse events are defined according to “Common Terminology Criteria for Adverse Events” (CTCAE), version 4.0. 5- Mobilizing potential: amount of CD34 + stem cell collected /Kg 6- Feasibility: proportion of randomized patients successfully completing ASCT ;Timepoint(s) of evaluation of this end point: 2 years of FU | — |
Countries
Italy
Contacts
Public ContactSegreteria FIL ONLUS
Fondazione Italiana Linfomi ONLUS
Outcome results
None listed