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

March 13, 2019 updated by: Boehringer Ingelheim

An Open Label Multicenter Phase Ib/II Trial to Determine the Dose of BI 836826 in Combination With Gemcitabine and Oxaliplatin (GemOx) and the Efficacy of BI 836826-GemOx Versus Rituximab (R)- GemOx (R-GemOx) in Patients With Relapsed/ Refractory Diffuse Large B-cell Lymphoma (DLBCL) Who Are Not Eligible for, or Have Relapsed/Progressed After Autologous/Allogeneic Stem Cell Transplant

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Hasselt, Belgium, 3500
        • Jessa Ziekenhuis - Campus Virga Jesse
  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Rozzano (MI), Italy, 20089
        • Istituto Clinico Humanitas
      • Udine, Italy, 33100
        • A. O. S. Maria della Misericordia
  • Spain
      • Badalona, Spain, 08916
        • Hospital Germans Trias i Pujol
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital La Paz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Age 18 years or older
  • Patients with histologically confirmed, relapsed/refractory, diffuse large B-cell lymphoma (including transformed follicular lymphoma) who have received an anti-CD20-supplemented, anthracycline-containing chemotherapy and are not eligible for high dose therapy followed by an autologous stem cell transplant, or have relapsed/progressed after autologous/allogenic stem cell transplant. Allogenic stem cell transplant performed at least 6 months prior to study entry is allowed if patients do not require immunosuppressive treatment and have no evidence of active graft-versus-host disease.
  • Patient has not received anti-lymphoma treatment prior to the first dose of trial medication: within past 14 days or within time that is shorter or equal to 5 half-lives of the drug if the last anti-lymphoma treatment contained an investigational agent
  • Screening computer tomography (CT) scan with involvement of at least 1 bi-dimensional lesion/node >1.5 cm
  • Screening [18F] fluorodeoxyglucose (FDG)- positron emission tomography (PET) scans must demonstrate positive lesion compatible with computer tomography (CT) defined anatomical tumor sites
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
  • Written signed informed consent consistent with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) and local legislation
  • Patients must have an acceptable organ function
  • Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. Non-vasectomized male patients having a female sexual partner of childbearing potential must ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least 12 months after the end of the trial.

Exclusion criteria:

  • Eligible for curative salvage high dose therapy followed by stem cell transplant
  • Primary central nervous system lymphoma or known Central nervous system (CNS) involvement
  • Prior history of malignancy other than DLBCL except basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the uterine cervix or breast which has been treated with curative therapy. Other prior malignancies are allowed only if patient has been free of disease and without treatment other than hormones for at least past three years.
  • Refractory to gemcitabine and/or oxaliplatin
  • Contraindications for gemcitabine, oxaliplatin and/or rituximab as judged by the investigator. Hypersensitivity to oxaliplatin
  • Unresolved toxicity of CTCAE grade > 1from prior anti-lymphoma therapy (except alopecia)
  • Significant concurrent medical disease or condition which according to the investigators judgment would either compromise patient safety or interfere with the evaluation of the safety of the test drug. e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy with the exception of extra systoles of minor conduction abnormalities
  • An infection requiring treatment at the start of the trial medication.
  • Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection or HIV infection (test results done in routine diagnostics are acceptable if done within 14 days before the first study treatment dose)
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial.This includes the female sexual partners of a male participant
  • Known alcohol or drug abuse which could potentially interfere with trial participation according to investigators judgment
  • Prior treatment with CD37 antibody

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BI 836826-GemOx
Drug: BI 836826
Drug: GemOx
Active Comparator: R-GemOx
Drug: Rituximab
Drug: GemOx

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period- Phase 1b
Time Frame: 14 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.
14 days from first trial medication
The MTD of BI 836826 With GemOx- Phase 1b
Time Frame: 14 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).
14 days from first trial medication
Overall Response, i.e. CR and PR, by Central Review Assessment- Phase II
Time Frame: up 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.
up to 32 weeks from first trial medication administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Based on Investigator's Assessment- Phase 1b
Time Frame: up 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
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
Time Frame: up 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.
up to 32 weeks from first trial medication administration.
Maximum Measured Plasma Concentration of BI 836826 (Cmax)- Phase 1b
Time Frame: up 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.
up to 32 weeks from first trial medication administration.
Complete Response (CR) by Central Review Assessment- Phase II
Time Frame: up 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.
up to 32 weeks from first trial medication administration.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2016

Primary Completion (Actual)

March 16, 2018

Study Completion (Actual)

March 16, 2018

Study Registration Dates

First Submitted

December 4, 2015

First Submitted That Met QC Criteria

December 4, 2015

First Posted (Estimate)

December 8, 2015

Study Record Updates

Last Update Posted (Actual)

June 17, 2019

Last Update Submitted That Met QC Criteria

March 13, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1270.11
  • 2014-004794-16 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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