Lymphoma, Large B-Cell, DiffusePhase 2NCT02624492
To Determine the Dose of BI 836826-GemOx and the Efficacy of BI 836826-GemOx Versus R-GemOx in Patients With Relapsed/Refractory DLBCL
A Phase 2 study testing BI 836826, GemOx and Rituximab in people with Lymphoma, Large B-Cell, Diffuse, run by Boehringer Ingelheim at 7 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Large B-Cell, Diffuse
- What is being tested?
- BI 836826, GemOx and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 28 Jan 2016to 16 Mar 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Italy3 sites
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Istituto Clinico Humanitas
Rozzano (MI), 20089
A. O. S. Maria della Misericordia
Udine, 33100
Spain3 sites
Hospital Germans Trias i Pujol
Badalona, 08916
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital La Paz
Madrid, 28046
About this study
Official title: 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:
Read more
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).
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Being tested
- BI 836826, GemOx, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 836826Drug
GemOxDrug
RituximabDrug
GemOxDrug
| Study group | Role | What they receive |
|---|---|---|
| BI 836826-GemOx | Experimental | Not described Receives: Drug: BI 836826; Drug: GemOx |
| R-GemOx | Active comparator | Not described Receives: Drug: Rituximab; Drug: GemOx |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: up to 32 weeks from first trial medication administration
Secondary outcomes (4)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: up to 32 weeks from first trial medication administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2015 (estimated)
- Study start28 Jan 2016
- Primary completion16 Mar 2018
- Study completion16 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoma, Large B-Cell, DiffuseStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02624492
- Sponsor's protocol ID
- 1270.11
- Other IDs
- 2014-004794-16, 2014
- Status last verified
- Mar 2019
- First submitted
- 4 Dec 2015
- Last updated
- 17 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02624492
- Acronym / sponsor ID
- 1270.11
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 28 Jan 2016 (actual)
- Primary completion
- 16 Mar 2018 (actual)
- Study completion
- 16 Mar 2018 (actual)
- First posted
- 8 Dec 2015 (estimated)
- Results
- Posted 17 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BI 836826-GemOx | Experimental | Drug: BI 836826, Drug: GemOx |
| R-GemOx | Active comparator | Drug: Rituximab, Drug: GemOx |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 836826 | Drug | BI 836826-GemOx |
| GemOx | Drug | BI 836826-GemOx |
| Rituximab | Drug | R-GemOx |
| GemOx | Drug | R-GemOx |
Primary outcome
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.
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).
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.
4 secondary outcomes
Overall Response Based on Investigator's Assessment- Phase 1b
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
Time frame: 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.
Complete Response (CR) by Central Review Assessment- Phase II
Time frame: up to 32 weeks from first trial medication administration.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BI 836826, GemOx and Rituximab in people with Lymphoma, Large B-Cell, Diffuse, run by Boehringer Ingelheim at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy, Spain, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2019.