Part 1 (Phase Ib) Primary objective: To establish the maximum tolerated dose (MTD) of BI 836826 in combination with GemOx. Secondary objectives: To evaluate pharmacokinetics of BI 836826 when given in combination with GemOx and to investigate preliminary efficacy in terms of the overall response rate based on investigator's assessment. Part 2 (Phase II randomized) Primary objective: To investigate the efficacy by means of the overall response rate (PR+ CR) based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to R-GemOx. Secondary objective: To investigate the efficacy by means of the complete remission rate based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to Rituximab + gemcitabine + oxaliplatin (RGemOx).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, Belgium
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Clinico Humanitas
Rozzano (MI), Italy
A. O. S. Maria della Misericordia
Udine, Italy
Hospital Germans Trias i Pujol
Badalona, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital La Paz
Madrid, Spain
Number of Patients With Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period- Phase 1b
DLT definition included both non-haematologic and haematologic drug-related Adverse events (AEs). Non-haematologic AEs of Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or higher qualified for DLTs with the following exceptions: laboratory abnormalities that could be corrected with treatment within 48 h; nausea, vomiting, or diarrhoea which resolved within 48 h with adequate treatment; neuropathy considered related to oxaliplatin; or an infusion-related reactions (IRR). For haematologic AEs, the following were considered DLTs: Grade 4 neutropenia lasting \>7 days (d) despite growth factors support; any febrile neutropenia which did not resolve within 48 hours with appropriate treatment; Grade 4 thrombocytopenia lasting \>7 d or Grade 3/4 thrombocytopenia with clinically significant bleeding; failure to recover platelets ≥75\*10\^9/litres (L) by 4 weeks after start of the cycle; or failure to recover neutrophils ≥1.0\*10\^9/L by 4 weeks after start of the cycle.
Time frame: 14 days from first trial medication
The MTD of BI 836826 With GemOx- Phase 1b
MTD defined as the highest dose studied for which the number of patients with dose-limiting toxicity (DLT) was 17% or less (i.e. not more than 1 of 6 patients) during the MTD evaluation period (Cycle 1).
Time frame: 14 days from first trial medication
Overall Response, i.e. CR and PR, by Central Review Assessment- Phase II
Overall response based on central review assessment, i.e. CR and PR by central review assessment; CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites. Sponsor discontinued the trial for strategic reasons. Consequently, Phase II of the trial was not conducted and hence the endpoint is not evaluated.
Time frame: up to 32 weeks from first trial medication administration
Overall Response Based on Investigator's Assessment- Phase 1b
Overall response based on investigator's assessment, i.e. partial remission (PR) and complete remission (CR) by investigator assessment; CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites
Time frame: up to 32 weeks from first trial medication administration.
Area Under the Plasma Concentration-time Curve Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point After Drug Administration (AUC0-tz) of BI 836826- Phase 1b
Pharmacokinetic (PK) analyses were planned to be performed. However, after encountering technical difficulties and discontinuation of the BI 836826 programme, the sponsor decided not to re-analyse the samples.
Time frame: up to 32 weeks from first trial medication administration.
Maximum Measured Plasma Concentration of BI 836826 (Cmax)- Phase 1b
Pharmacokinetic analyses were planned to be performed. However, after encountering technical difficulties and discontinuation of the BI 836826 programme, the sponsor decided not to re-analyse the samples.
Time frame: up to 32 weeks from first trial medication administration.
Complete Response (CR) by Central Review Assessment- Phase II
Complete Response (CR) by central review assessment- Phase II; CR: Disappearance of all evidence of disease. Sponsor discontinued the trial for strategic reasons. Consequently, Phase II of the trial was not conducted and hence the endpoint is not evaluated.
Time frame: up to 32 weeks from first trial medication administration.
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