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To Determine the Dose of BI 836826-GemOx and the Efficacy of BI 836826-GemOx Versus R-GemOx in Patients With Relapsed/Refractory DLBCL

Phase 2
Completed
Conditions
Lymphoma, Large B-Cell, Diffuse
Interventions
Registration Number
NCT02624492
Lead Sponsor
Boehringer Ingelheim
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
21
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
R-GemOxGemOx-
BI 836826-GemOxGemOx-
BI 836826-GemOxBI 836826-
R-GemOxRituximab-
Primary Outcome Measures
NameTimeMethod
Overall Response, i.e. CR and PR, by Central Review Assessment- Phase IIup to 32 weeks from first trial medication administration

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.

Number of Patients With Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period- Phase 1b14 days from first trial medication

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.

The MTD of BI 836826 With GemOx- Phase 1b14 days from first trial medication

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).

Secondary Outcome Measures
NameTimeMethod
Overall Response Based on Investigator's Assessment- Phase 1bup to 32 weeks from first trial medication administration.

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

Maximum Measured Plasma Concentration of BI 836826 (Cmax)- Phase 1bup to 32 weeks from first trial medication administration.

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.

Complete Response (CR) by Central Review Assessment- Phase IIup to 32 weeks from first trial medication administration.

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.

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 1bup to 32 weeks from first trial medication administration.

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.

Trial Locations

Locations (7)

Hospital La Paz

🇪🇸

Madrid, Spain

Hospital Germans Trias i Pujol

🇪🇸

Badalona, Spain

Fondazione IRCCS Istituto Nazionale dei Tumori

🇮🇹

Milano, Italy

Jessa Ziekenhuis - Campus Virga Jesse

🇧🇪

Hasselt, Belgium

A. O. S. Maria della Misericordia

🇮🇹

Udine, Italy

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Istituto Clinico Humanitas

🇮🇹

Rozzano (MI), Italy

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