BI 836826 Dose Escalation in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (NHL)

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

A Phase I, Open-Label, Dose-Escalation Trial With BI 836826 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma of B Cell Origin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01403948
• Other study ID #: 1270.2
• Secondary ID: 2010-024456-29
• Status: Completed
• Phase: Phase 1
• Start date: August 1, 2011
• Est. completion date: February 28, 2018

Study information

• Verified date: August 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 28, 2018
• Est. primary completion date: November 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• BI 836826
Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion

Locations

Country	Name	City	State
France	INS Paoli-Calmettes	Marseille Cedex 09
France	HOP Lyon Sud	Pierre Bénite
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main
Germany	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Ulm	Ulm
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

France,  Germany,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From the first administration of trial medication to 7 days after the second administration, upto 36 days
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).	From the first administration of trial medication to 7 days after the second administration, up to 36 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.	Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25.
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.: Complete remission (CR); Complete remission unconfirmed (CRu); Partial remission (PR); Stable disease (SD); progressive disease (PD)	Screening, Week 1, Week 4, Week 7, Week 8, Week 11, Week 14, Week 15, Week 18 and at End of Treatment (EOT)
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.: Complete remission; Complete remission unconfirmed; Partial remission; Stable disease: progressive disease	Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25.
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.	from first treatment until disease progression or death from any cause, up to 12 months.
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.	from first treatment with BI 836826 until objective disease progression, death, or start of next NHL therapy, up to 12 months.

External Links

•   Related Info