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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BI 836826

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

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
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
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)
Relapse or progression of disease with an indication for therapy as per investigator's judgement
Life expectancy of =3 months
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

Exclusion criteria:

Primary central nervous system (CNS) lymphoma or known CNS involvement
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
Last chemotherapy <4 weeks prior to visit 1
Last anti-CD20 therapy (non-radiolabelled) <4 weeks prior to visit 1
Last corticosteroid <2 weeks prior to visit 1 unless the dose is less or equal of 10 mg/day prednisolone or equivalent
High-dose therapy with stem cell support <6 months prior to visit 1
Radio-immunotherapy <3 months prior to visit 1

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with relapsed or refractory NHL

Arm Description

Adult patients with relapsed or refractory non-Hodgkin lymphoma of B cell origin after at least two prior treatments

Outcomes

Primary Outcome Measures

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.

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).

Secondary Outcome Measures

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.

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)

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

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.

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.

Full Information

NCT ID

NCT01403948

First Posted

July 26, 2011

Last Updated

August 10, 2020

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01403948

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

August 1, 2011 (Actual)

Primary Completion Date

November 14, 2017 (Actual)

Study Completion Date

February 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Non-Hodgkin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients with relapsed or refractory NHL

Arm Type

Experimental

Arm Description

Adult patients with relapsed or refractory non-Hodgkin lymphoma of B cell origin after at least two prior treatments

Intervention Type

Drug

Intervention Name(s)

BI 836826

Intervention Description

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

Primary Outcome Measure Information:

Title

Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in First Cycle in Caucasian Patients

Description

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

Title

Number of Subjects With Dose Limiting Toxicities (DLT) in First Cycle in Caucasian Patients

Description

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

Secondary Outcome Measure Information:

Title

Tumour Size Reduction

Description

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.

Title

Best Overall Response Based on All Assessment

Description

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)

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)

Title

Best Overall Response Based on Imaging Data

Description

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

Time Frame

Computed tomography (CT) scan performed at screening, at Week 13, and at Week 25.

Title

Progression Free Survival (PFS)

Description

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.

Title

Failure Free Survival (FFS)

Description

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion criteria: 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 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 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) Relapse or progression of disease with an indication for therapy as per investigator's judgement Life expectancy of =3 months Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Exclusion criteria: Primary central nervous system (CNS) lymphoma or known CNS involvement 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 Last chemotherapy <4 weeks prior to visit 1 Last anti-CD20 therapy (non-radiolabelled) <4 weeks prior to visit 1 Last corticosteroid <2 weeks prior to visit 1 unless the dose is less or equal of 10 mg/day prednisolone or equivalent High-dose therapy with stem cell support <6 months prior to visit 1 Radio-immunotherapy <3 months prior to visit 1

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

INS Paoli-Calmettes

City

Marseille Cedex 09

ZIP/Postal Code

13273

Country

France

Facility Name

HOP Lyon Sud

City

Pierre Bénite

ZIP/Postal Code

69495

Country

France

Facility Name

Charité - Universitätsmedizin Berlin

City

Berlin

ZIP/Postal Code

12200

Country

Germany

Facility Name

Universitätsklinikum Carl Gustav Carus Dresden

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Universitätsklinikum Frankfurt

City

Frankfurt am Main

ZIP/Postal Code

60590

Country

Germany

Facility Name

Universitätsmedizin Göttingen, Georg-August-Universität

City

Göttingen

ZIP/Postal Code

37075

Country

Germany

Facility Name

Asklepios Klinik St. Georg

City

Hamburg

ZIP/Postal Code

20099

Country

Germany

Facility Name

Universitätsklinikum Heidelberg

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Universitätsklinikum Jena

City

Jena

ZIP/Postal Code

07740

Country

Germany

Facility Name

Universitätsklinikum Ulm

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

32172489

Citation

Kroschinsky F, Middeke JM, Janz M, Lenz G, Witzens-Harig M, Bouabdallah R, La Rosee P, Viardot A, Salles G, Kim SJ, Kim TM, Ottmann O, Chromik J, Quinson AM, von Wangenheim U, Burkard U, Berk A, Schmitz N. Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Invest New Drugs. 2020 Oct;38(5):1472-1482. doi: 10.1007/s10637-020-00916-3. Epub 2020 Mar 14. Erratum In: Invest New Drugs. 2020 May 31;: Invest New Drugs. 2020 Jun 23;:

Results Reference

derived

Links:

URL

http://trials.boehringer-ingelheim.com

Description

Related Info

Lymphoma, Non-Hodgkin

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial