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

Phase 1
Completed
Conditions
Lymphoma, Non-Hodgkin
Interventions
Registration Number
NCT01403948
Lead Sponsor
Boehringer Ingelheim
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Patients with relapsed or refractory NHLBI 836826Adult patients with relapsed or refractory non-Hodgkin lymphoma of B cell origin after at least two prior treatments
Primary Outcome Measures
NameTimeMethod
Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in First Cycle in Caucasian PatientsFrom 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 PatientsFrom 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 Outcome Measures
NameTimeMethod
Tumour Size ReductionComputed 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.

Best Overall Response Based on All AssessmentScreening, 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)

Best Overall Response Based on Imaging DataComputed 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

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.

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.

Trial Locations

Locations (12)

HOP Lyon Sud

🇫🇷

Pierre Bénite, France

Asklepios Klinik St. Georg

🇩🇪

Hamburg, Germany

Universitätsklinikum Carl Gustav Carus Dresden

🇩🇪

Dresden, Germany

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Universitätsklinikum Frankfurt

🇩🇪

Frankfurt am Main, Germany

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Universitätsmedizin Göttingen, Georg-August-Universität

🇩🇪

Göttingen, Germany

Universitätsklinikum Jena

🇩🇪

Jena, Germany

INS Paoli-Calmettes

🇫🇷

Marseille Cedex 09, France

Charité - Universitätsmedizin Berlin

🇩🇪

Berlin, Germany

Universitätsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Universitätsklinikum Ulm

🇩🇪

Ulm, Germany

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