Patients with relapsed/refractory diffuse large B-cell lymphoma including transformed follicular lymphoma) who have been previously treated with an anti-CD20 monoclonal antibody (e.g. rituximab) in combination with an anthracycline containing chemotherapy and who are not eligible for, or have relapsed/progressed after autologous/allogeneic stem cell transplant MedDRA version: 20.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104
Conditions
Interventions
Product Name: BI 836826
Product Code: BI 836826
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: -
CAS Number: -
Current Sponsor code: BI 836826
Other descriptive name:
Sponsors
SCS Boehringer Ingelheim Comm. V
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older 2. Patients with histologically confirmed, relapsed/refractory, diffuse large B-cell lymphoma (including transformed follicular lymphoma) o who have received an anti-CD20-supplemented, anthracycline-containing chemotherapy and o are not eligible for high dose therapy followed by an autologous stem cell transplant, or have relapsed/progressed after autologous/ allogeneic 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. 3. Patient has not received anti-lymphoma treatment prior to the first dose of trial medication: o within past 14 days or o within time that is shorter or equal to 5 half-lives of the drug if the last anti-lymphoma treatment contained an investigational agent 4. Screening computer tomography (CT) scan with involvement of at least 1 bi-dimensional lesion/node >1.5cm 5. Screening [18F] flourodeoxyglucose (FDG)- positron emission tomography (PET) scans must demonstrate positive lesion compatible with computer tomography (CT) defined anatomical tumor sites. 6. ECOG performance status 0, 1, 2 7. Written signed informed consent consistent with ICH GCP and local legislation 8. Patients must have an acceptable organ function 9. 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 128
Exclusion criteria
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 investigator's judgment ? Prior treatment with CD37 antibody
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 (Phase Ib) To establish the maximum tolerated dose (MTD) of BI 836826 in combination with GemOx. Part 2 (Phase II randomized) To investigate the efficaccy by means of the overall response rate (PR+CR) based on central review assessment in patients with relapsed DLBCL treated with BI 86826-GemOx xompared to R-GemOx.;Secondary Objective: Parr 1 (Phase Ib) 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) To investigate the efficacy by meons of the complete remission rate based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to R-GemOx.;Primary end point(s): Part 1 1: The number of patients with DLTs in cycle 1. 2: The MTD of BI 836826 with GemOx based on the number of evaluable patients with DLTs in cycle 1. The MTD of BI 836826 with GemOx is defined as the highest dose studied for which the number of evaluable patients with dose-limiting toxicity is 17% or less (i.e., 0-1/6 patients) during cycle 1. Part 2 1: Overall response (OR) by central review assessment, i.e. partial response (PR) and complete remission (CR) by central review assessment, analyzed by the ORR and compared between the two treatment arms. ;Timepoint(s) of evaluation of this end point: Part 1: 14 days from first trial medication administration Part 2: up to 32 weeks from first trial medication administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 1: The secondary endpoint will be pharmacokinetic parameters: AUCt and Cmax of BI 836826 when administered in combination with GemOx 2: Overall response based on investigator's assessment. Part 2 1: The CR by central review assessment will be the secondary endpoint, and will be compared between the two treatment arms.;Timepoint(s) of evaluation of this end point: Part 1 + 2: up to 32 weeks from first trial medication administration | — |
Countries
Belgium, Canada, France, Germany, Hungary, Italy, Korea, Democratic People's Republic of, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed