Phase I Dose Escalation of i.v. BI 836909 Monotherapy in Last Line Multiple Myeloma Patients
- Conditions
- Multiple Myeloma
- Interventions
- Drug: BI 836909
- Registration Number
- NCT02514239
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this trial is to determine the maximum tolerated dose (MTD) of BI 836909 administered by continuous i.v. infusion in patients with relapsed and/or refractory multiple myeloma. If the MTD is not reached based on safety findings, a recommended dose for further development will be determined. This will depend on the safety data, pharmacokinetic/pharmacodynamics data and potentially preliminary efficacy data. Secondary objectives are to document the safety and tolerability of BI 836909, to perform pharmacokinetic and pharmacodynamic analyses and to evaluate relevant biological effects in terms of parameters of efficacy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Intravenous Infusion of BI 836909 (3.2 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (13 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (25 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (50 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (400 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (100 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (200 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (800 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (0.2 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (0.8 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (0.4 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (1.6 μg/d) BI 836909 - Intravenous Infusion of BI 836909 (6.5 μg/d) BI 836909 -
- Primary Outcome Measures
Name Time Method The Maximum Tolerated Dose (MTD) of BI 836909 Cycle 1, up to 6 weeks. The Maximum tolerated dose (MTD) of BI 836909, which was defined as the highest dose of the dose level tested where ≤1 patient out of 6 developed a Dose-limiting toxicity (DLT). The MTD was defined based on DLTs observed during Cycle 1. However, all Adverse Events corresponding to the definition of a DLT (see below) were to be considered for confirming the MTD. A DLT was defined as any drug-related non-haematological Adverse Event of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher.
The Number of Patients With Dose-limiting Toxicities (DLTs) Cycle 1, up to 6 weeks. The number of patients with Dose-limiting toxicities (DLTs) in cycle 1. A Dose-limiting toxicity was defined as any drug-related non-haematological Adverse Event of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher.
- Secondary Outcome Measures
Name Time Method Number of Participants With an Objective Response On-treatment: From start of treatment till end of trial (EOT) visit, up to 61 weeks. Extended follow-up: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. Objective responses: Stringent complete response (sCR): CR + normal Free light chain (FLC) ratio and no clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. Very good partial response (VGPR): serum and urine M protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M protein plus urine M protein level \<100 mg/24h. PR: \>50% reduction of serum and 24 h urinary M protein by \>90% or to \<200mg/24h. If unmeasurable, a \>50% decrease in difference between involved and uninvolved FLC levels instead of M protein criteria. if FLC assay was not measurable, a \>50% reduction in plasma cells was required instead of M protein, provided baseline bone marrow plasma cell was \>30%. In addition to the listed criteria, a \>50% reduction in the size of soft tissue plasmacytomas was also required, if present at baseline.
Duration of Objective Response - on Treatment From start of treatment till end of trial (EOT) visit, up to 61 weeks. For patients with objective response, the duration of response was calculated from the time of first recorded achievement of a response (sCR, CR, PR, or VGPR) until documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Duration of Objective Response - Including Extended Follow up Visits From start of treatment till the last extended follow-up visit which is scheduled at 12 months after end of treatment, up to 113 weeks. For patients with objective response, the duration of response was calculated from the time of first recorded achievement of a response (sCR, CR, PR, or VGPR) until documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Number of Participants With a Minimal Residual Disease (MRD) Response On-treatment: From start of treatment till end of trial (EOT) visit, up to 61 weeks. Follow-up: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. Minimal residual disease (MRD) response was defined as \<1 tumour cell within 10000 normal cells in bone marrow. MRD was determined using Fluorescence-activated cell sorting (FACS) analysis.
Duration of Minimal Residual Disease (MRD) Response - on Treatment From start of treatment till end of trial (EOT) visit, up to 61 weeks. Duration of MRD response was calculated from the time of first recorded achievement of a MRD response to documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Duration of Minimal Residual Disease (MRD) Response - Including Extended Follow up Visits From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. Duration of MRD response was calculated from the time of first recorded achievement of a MRD response to documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Progression-free Survival (PFS) - on Treatment From start of treatment till end of trial (EOT) visit, up to 61 weeks. PFS was defined as time from first treatment with BI 836909 till disease progression or death. Progression was defined according to International Myeloma Working Group (IMWG 2006) response criteria as an increase \>25% from lowest response value in any of the following parameters: -Serum M protein (absolute increase had to be \>0.5 gram/ deciliters (dL)) -Urine M protein (absolute increase had to be \>200 milligram (mg)/24 hour) -Only in patients without measurable serum and urine M protein levels The difference between involved and uninvolved FLC levels. Absolute increase had to be \>10 mg/dL -Bone marrow plasma cell percentage; absolute percentage had to be \>10% -Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas -Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 Millimole/Liter) that was attributed solely to the plasma cell proliferative disorder.
Progression-free Survival (PFS) - Including Extended Follow up Visits From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. PFS was defined as time from first treatment with BI 836909 till disease progression or death. Progression was defined according to International Myeloma Working Group (IMWG 2006) response criteria as an increase \>25% from lowest response value in any of the following parameters: -Serum M protein (absolute increase had to be \>0.5 gram/ deciliters (dL)) -Urine M protein (absolute increase had to be \>200 milligram (mg)/24 hour) -Only in patients without measurable serum and urine M protein levels The difference between involved and uninvolved FLC levels. Absolute increase had to be \>10 mg/dL -Bone marrow plasma cell percentage; absolute percentage had to be \>10% -Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas -Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 Millimole/Liter) that was attributed solely to the plasma cell proliferative disorder
Serum Concentration at Steady State of BI 836909 (Css) Pharmacokinetic samples were collected at 48:00 hours (h):minutes (min), 168:00, 336:00, 504:00 and 671:50 h after the start of infusion of BI 836909 of the first cycle. Serum concentration at steady state of BI 836909 (Css).
Trial Locations
- Locations (5)
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
HOP Hôtel-Dieu
🇫🇷Nantes, France
HOP Claude Huriez
🇫🇷Lille, France
INS Universitaire du Cancer
🇫🇷Toulouse, France