Lymphoma, Non-Hodgkin
Conditions
Brief summary
The purpose is to investigate the maximum tolerated dose (MTD), safety and tolerability, pharmacokinetics and efficacy of BI 836826 monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma with at least prior treatments.
Interventions
DRUGBI 836826
Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion
Sponsors
Boehringer Ingelheim
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with relapsed or refractory non-Hodgkin lymphoma of B cell origin (mature B cell lymphoma according to WHO) not considered candidates for intensive anti-lymphoma therapy 2. Patients must have either aggressive NHL and received at least one prior anti-CD20 containing immunochemotherapy or indolent NHL and received anti-CD20 therapy and at least two prior therapies 3. Measurable disease on computed tomography (CT) scan with involvement of one clearly demarcated lesion =2 cm or two or more clearly demarcated lesions of \>1.5 cm at longest diameter (this criterion applies only for the expansion cohort) 4. Relapse or progression of disease with an indication for therapy as per investigator's judgement 5. Life expectancy of =3 months 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Exclusion criteria
1. Primary central nervous system (CNS) lymphoma or known CNS involvement 2. Prior history of malignancy other than a mature B cell neoplasm according to WHO classification (except basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the uterine cervix or breast treated with curative therapy) unless the subject has been free of disease and without treatment for at least 5 years 3. Last chemotherapy \<4 weeks prior to visit 1 4. Last anti-CD20 therapy (non-radiolabelled) \<4 weeks prior to visit 1 5. Last corticosteroid \<2 weeks prior to visit 1 unless the dose is less or equal of 10 mg/day prednisolone or equivalent 6. High-dose therapy with stem cell support \<6 months prior to visit 1 7. Radio-immunotherapy \<3 months prior to visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in First Cycle in Caucasian Patients | From the first administration of trial medication to 7 days after the second administration, upto 36 days | The primary objective of the dose-escalation part of this study was to determine the MTD of BI 836826 in caucasian patients. The MTD was to be defined on the basis of DLTs observed during the first 2 weeks of the 1st treatment course. In case of a delay of the second administration, evaluation of DLT was to be prolonged to 7 days after the second administration.. A DLT was defined as any drug-related non-haematological Adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher, except Infusion-related reaction (IRRs) associated with the administration of BI 836826. |
| Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | From the first administration of trial medication to 7 days after the second administration, up to 36 days | Number of subjects with Dose Limiting Toxicities (DLT) in first Cycle during the MTD evaluation period in caucasian patients with relapsed or refractory Non-Hodgkin lymphoma (NHL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Based on Imaging Data | Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25. | Best overall response based on imaging data. Response was assessed as follow according to the Standardized or Revised Response Criteria for Malignant Lymphoma from 1999.: 1. Complete remission 2. Complete remission unconfirmed 3. Partial remission 4. Stable disease: 5. progressive disease |
| Tumour Size Reduction | Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25. | Tumour size reduction (lymph nodes, spleen, & liver nodules) defined as best percentage change from baseline in sum of products of diameter (SPD). Negative value represents decrease in tumour size, & positive value represents an increase in size. The tumour size of lymph nodes was to be measured as SPD of 2 perpendicular dimensions for up to 6 indicator lesions identified at baseline CT scan. Spleen & liver were to be described if considered enlarged at baseline by physical examination or CT scan. If nodules present in spleen &/or liver, was to be measured in 2 perpendicular dimensions. Median, 25th & 75th percentiles are calculated from unadjusted Kaplan-Meier curve for each treatment cohort. |
| Failure Free Survival (FFS) | from first treatment with BI 836826 until objective disease progression, death, or start of next NHL therapy, up to 12 months. | FFS was defined as the time from first treatment with BI 836826 until objective disease progression, death, or start of next Non-Hodgkin lymphoma (NHL) therapy.For disease progression one of the following criteria was required: • Any new lesion \>1.5 centimeter (cm) in any axis • Increase of ≥50% from nadir in sum of product of diameter of any previously involved nodes or single nodes or the size of hepatic or splenic nodules. A lymph node with a diameter of the short axis of \<1 cm had to increase by ≥50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis • Increase of ≥50% in the longest diameter of any single previously identified node \>1 cm in its short axis. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment cohort. |
| Progression Free Survival (PFS) | from first treatment until disease progression or death from any cause, up to 12 months. | PFS was defined as the time from first treatment with BI 836826 until disease progression or death from any cause. For disease progression one of the following criteria was required: • Any new lesion \>1.5 centimeter (cm) in any axis • Increase of ≥50% from nadir in sum of product of diameter of any previously involved nodes or single nodes or the size of hepatic or splenic nodules. A lymph node with a diameter of the short axis of \<1 cm had to increase by ≥50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis • Increase of ≥50% in the longest diameter of any single previously identified node \>1 cm in its short axis. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment cohort. |
| Best Overall Response Based on All Assessment | Screening, Week 1, Week 4, Week 7, Week 8, Week 11, Week 14, Week 15, Week 18 and at End of Treatment (EOT) | Best overall response was best response at any of CT scans and investigator assesment (incase the recent CT scan was not available). Response was assessed as follow according to the Standardized or Revised Response Criteria for Malignant Lymphoma from 1999.: 1. Complete remission (CR) 2. Complete remission unconfirmed (CRu) 3. Partial remission (PR) 4. Stable disease (SD) 5. progressive disease (PD) |
Countries
France, Germany, South Korea
Participant flow
Recruitment details
This was an open-label trial with a dose-escalation phase according to a modified 3+3 design.
Pre-assignment details
All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be entered to trial drug if any of the specific entry criteria was violated.
Participants by arm
| Arm | Count |
|---|---|
| BI 836826 1 mg iv (Caucasian Patients) BI 836826 1 milligram (mg) was administered as an intravenous (iv) infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 1 |
| BI 836826 3 mg iv (Caucasian Patients) BI 836826 3 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 4 |
| BI 836826 9 mg iv (Caucasian Patients) BI 836826 9 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 3 |
| BI 836826 25 mg iv (Caucasian Patients) BI 836826 25 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 4 |
| BI 836826 50 mg iv (Caucasian Patients) BI 836826 50 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 6 |
| BI 836826 50mg iv (Korean Patients) BI 836826 50 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in korean patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 7 |
| BI 836826 100 mg iv (Caucasian Patients) BI 836826 100 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 6 |
| BI 836826 100 mg iv (Korean Patients) BI 836826 100 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in korean patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 4 |
| BI 836826 150 mg iv (Caucasian Patients) BI 836826 150 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 6 |
| BI 836826 200 mg iv (Caucasian Patients) BI 836826 200 mg was administered as an intravenous infusion anytime in day (preferably morning hours) in caucasian patients with relapsed or refractory non-hodgkin lymphoma of B cell origin.
Each course was to comprise 4 administrations at weekly intervals, followed by 27 days of observation after last administration. The duration of the 2 first courses was 7 weeks each and the duration of the 3rd course was 12 weeks. The maximum duration of the treatment and observation/rest periods was 26 weeks. | 7 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other Adverse Event (Other than DLT) | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 1 | 0 |
| Overall Study | other than above | 1 | 2 | 1 | 0 | 1 | 1 | 2 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 0 | 2 | 2 | 4 | 2 | 6 | 2 | 4 | 5 | 5 |
| Overall Study | Refused cont. medication | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | BI 836826 200 mg iv (Caucasian Patients) | Total | BI 836826 150 mg iv (Caucasian Patients) | BI 836826 100 mg iv (Korean Patients) | BI 836826 100 mg iv (Caucasian Patients) | BI 836826 50mg iv (Korean Patients) | BI 836826 50 mg iv (Caucasian Patients) | BI 836826 25 mg iv (Caucasian Patients) | BI 836826 9 mg iv (Caucasian Patients) | BI 836826 3 mg iv (Caucasian Patients) | BI 836826 1 mg iv (Caucasian Patients) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 68.0 Years | 68.5 Years | 66.0 Years | 70.0 Years | 69.0 Years | 57.0 Years | 74.5 Years | 69.5 Years | 61.0 Years | 75.0 Years | 75.0 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 11 Participants | 0 Participants | 4 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 33 Participants | 4 Participants | 0 Participants | 6 Participants | 0 Participants | 6 Participants | 4 Participants | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Female | 3 Participants | 18 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 30 Participants | 5 Participants | 1 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 4 | 1 / 3 | 1 / 4 | 2 / 6 | 1 / 7 | 1 / 6 | 1 / 4 | 2 / 6 | 1 / 7 |
| other Total, other adverse events | 1 / 1 | 4 / 4 | 3 / 3 | 4 / 4 | 6 / 6 | 7 / 7 | 6 / 6 | 4 / 4 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 0 / 1 | 3 / 4 | 2 / 3 | 1 / 4 | 5 / 6 | 4 / 7 | 5 / 6 | 3 / 4 | 3 / 6 | 5 / 7 |
Outcome results
Primary
Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in First Cycle in Caucasian Patients
The primary objective of the dose-escalation part of this study was to determine the MTD of BI 836826 in caucasian patients. The MTD was to be defined on the basis of DLTs observed during the first 2 weeks of the 1st treatment course. In case of a delay of the second administration, evaluation of DLT was to be prolonged to 7 days after the second administration.. A DLT was defined as any drug-related non-haematological Adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher, except Infusion-related reaction (IRRs) associated with the administration of BI 836826.
Time frame: From the first administration of trial medication to 7 days after the second administration, upto 36 days
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 836826 | Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in First Cycle in Caucasian Patients | 100 Milligram (mg) |
Primary
Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients
Number of subjects with Dose Limiting Toxicities (DLT) in first Cycle during the MTD evaluation period in caucasian patients with relapsed or refractory Non-Hodgkin lymphoma (NHL).
Time frame: From the first administration of trial medication to 7 days after the second administration, up to 36 days
Population: Treated Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 836826 | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 0 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 3 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients | 1 Participants |
Secondary
Best Overall Response Based on All Assessment
Best overall response was best response at any of CT scans and investigator assesment (incase the recent CT scan was not available). Response was assessed as follow according to the Standardized or Revised Response Criteria for Malignant Lymphoma from 1999.: 1. Complete remission (CR) 2. Complete remission unconfirmed (CRu) 3. Partial remission (PR) 4. Stable disease (SD) 5. progressive disease (PD)
Time frame: Screening, Week 1, Week 4, Week 7, Week 8, Week 11, Week 14, Week 15, Week 18 and at End of Treatment (EOT)
Population: Treated set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 836826 | Best Overall Response Based on All Assessment | Missing | 0 Participants |
| BI 836826 | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 | Best Overall Response Based on All Assessment | Stable disease | 1 Participants |
| BI 836826 | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 | Best Overall Response Based on All Assessment | Progressive disease | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 1 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 3 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 1 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 2 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 2 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 2 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 1 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 1 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 1 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 3 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 3 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 1 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 3 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 3 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 2 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 1 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 2 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 2 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 1 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 5 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Missing | 1 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Progressive disease | 4 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Complete remission unconfirmed | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Partial remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on All Assessment | Stable disease | 2 Participants |
Secondary
Best Overall Response Based on Imaging Data
Best overall response based on imaging data. Response was assessed as follow according to the Standardized or Revised Response Criteria for Malignant Lymphoma from 1999.: 1. Complete remission 2. Complete remission unconfirmed 3. Partial remission 4. Stable disease: 5. progressive disease
Time frame: Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25.
Population: Treated set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 836826 | Best Overall Response Based on Imaging Data | Progressive disease | 0 Participants |
| BI 836826 | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 | Best Overall Response Based on Imaging Data | Missing | 0 Participants |
| BI 836826 | Best Overall Response Based on Imaging Data | Stable disease | 1 Participants |
| BI 836826 | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 2 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 1 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 1 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 3 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 2 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 9 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 1 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 4 Participants |
| BI 836826 25 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 3 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 1 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 50 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 2 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 1 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 1 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 5 Participants |
| BI 836826 100 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 2 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 1 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 1 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 2 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 4 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 5 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 1 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
| BI 836826 150 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Partial remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Progressive disease | 4 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission | 0 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Missing | 1 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Stable disease | 2 Participants |
| BI 836826 200 mg iv (Caucasian Patients) | Best Overall Response Based on Imaging Data | Complete remission unconfirmed | 0 Participants |
Secondary
Failure Free Survival (FFS)
FFS was defined as the time from first treatment with BI 836826 until objective disease progression, death, or start of next Non-Hodgkin lymphoma (NHL) therapy.For disease progression one of the following criteria was required: • Any new lesion \>1.5 centimeter (cm) in any axis • Increase of ≥50% from nadir in sum of product of diameter of any previously involved nodes or single nodes or the size of hepatic or splenic nodules. A lymph node with a diameter of the short axis of \<1 cm had to increase by ≥50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis • Increase of ≥50% in the longest diameter of any single previously identified node \>1 cm in its short axis. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment cohort.
Time frame: from first treatment with BI 836826 until objective disease progression, death, or start of next NHL therapy, up to 12 months.
Population: Treated set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836826 | Failure Free Survival (FFS) | 352.00 days |
| BI 836826 3 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 87.00 days |
| BI 836826 9 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 81.00 days |
| BI 836826 25 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 22.00 days |
| BI 836826 50 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 85.00 days |
| BI 836826 100 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 25.00 days |
| BI 836826 150 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 200.00 days |
| BI 836826 200 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 51.50 days |
| BI 836826 150 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 34.00 days |
| BI 836826 200 mg iv (Caucasian Patients) | Failure Free Survival (FFS) | 36.00 days |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from first treatment with BI 836826 until disease progression or death from any cause. For disease progression one of the following criteria was required: • Any new lesion \>1.5 centimeter (cm) in any axis • Increase of ≥50% from nadir in sum of product of diameter of any previously involved nodes or single nodes or the size of hepatic or splenic nodules. A lymph node with a diameter of the short axis of \<1 cm had to increase by ≥50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis • Increase of ≥50% in the longest diameter of any single previously identified node \>1 cm in its short axis. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment cohort.
Time frame: from first treatment until disease progression or death from any cause, up to 12 months.
Population: Treated set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836826 | Progression Free Survival (PFS) | 352.00 days |
| BI 836826 3 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 87.00 days |
| BI 836826 9 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 81.00 days |
| BI 836826 25 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 22.00 days |
| BI 836826 50 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 262.00 days |
| BI 836826 100 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 27.50 days |
| BI 836826 150 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 200.00 days |
| BI 836826 200 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 51.50 days |
| BI 836826 150 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 34.00 days |
| BI 836826 200 mg iv (Caucasian Patients) | Progression Free Survival (PFS) | 38.00 days |
Secondary
Tumour Size Reduction
Tumour size reduction (lymph nodes, spleen, & liver nodules) defined as best percentage change from baseline in sum of products of diameter (SPD). Negative value represents decrease in tumour size, & positive value represents an increase in size. The tumour size of lymph nodes was to be measured as SPD of 2 perpendicular dimensions for up to 6 indicator lesions identified at baseline CT scan. Spleen & liver were to be described if considered enlarged at baseline by physical examination or CT scan. If nodules present in spleen &/or liver, was to be measured in 2 perpendicular dimensions. Median, 25th & 75th percentiles are calculated from unadjusted Kaplan-Meier curve for each treatment cohort.
Time frame: Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25.
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BI 836826 | Tumour Size Reduction | indicator lesions | -44.74 Percentage | — |
| BI 836826 3 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | 118.42 Percentage | Standard Deviation 183.49 |
| BI 836826 9 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | -0.11 Percentage | Standard Deviation 61.72 |
| BI 836826 25 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | 67.26 Percentage | Standard Deviation 61.78 |
| BI 836826 50 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | -3.72 Percentage | Standard Deviation 10.19 |
| BI 836826 100 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | 28.80 Percentage | Standard Deviation 78.03 |
| BI 836826 150 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | -9.44 Percentage | Standard Deviation 34.49 |
| BI 836826 200 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | 110.88 Percentage | Standard Deviation 41.82 |
| BI 836826 150 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | 60.13 Percentage | Standard Deviation 29.68 |
| BI 836826 200 mg iv (Caucasian Patients) | Tumour Size Reduction | indicator lesions | 1.90 Percentage | — |
| BI 836826 200 mg iv (Caucasian Patients) | Tumour Size Reduction | liver nodules | 33.16 Percentage | — |