Safety and Dose Determining Multi-dose Study of BT062 in Patients With Relapsed or Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT01001442|
Recruitment Status : Completed
First Posted : October 26, 2009
Results First Posted : May 8, 2018
Last Update Posted : July 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: BT062||Phase 1 Phase 2|
Phase I/IIa, open-label, 3 + 3 multi-dose escalation study. The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.
The Phase IIa part was to include the MTD/recommended phase II dose (RPTD) expansion cohort in which descriptive statistical methods for evaluation of response, time to event endpoints, and safety were to be performed.
35 subjects in the Safety population, 34 subjects in the ITT and PP populations.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/IIa Multi-Dose Escalation Study to Evaluate Maximum Tolerated Dose (MTD), Pharmacokinetics (PK), Safety and Efficacy of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||July 2014|
|Actual Study Completion Date :||March 2016|
BT062 was to be administered as single-dose IV infusions via a 0.22 μm in-line filter preferably in a forearm vein, according to medically accepted procedures on Days 1, 8, and 15 of each 28-day cycle. Alternatively BT062 may have been administered through a central venous line or a peripherally inserted central catheter (PICC). Other administration routes were only to be allowed after approval from Biotest. Each subject was to be monitored carefully for the effects of exposure to BT062. No subject was to have received more than 3 doses of BT062 per 28-day treatment cycle.
Other Name: Indatuximab ravtansine
- Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT [ Time Frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months) ]The primary safety variable was to determine the incidence of DLTs in subjects with relapsed or relapsed/refractory multiple myeloma treated with BT062.
- Maximum Tolerated Dose (MTD) [ Time Frame: First 28-day cycle ]
The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.
Only DLTs occurring in cycle 1 for each subject were counted in the dose escalation decisions.
Three subjects were treated at the first or newest dose level as available. If none of the 3 subjects experienced a DLT during Cycle 1, three subjects could be treated at the next dose level as available.
In case of a DLT the cohort was expanded to up to 6 subjects. If not more than 1 of these 6 subjects experienced a DLT during Cycle 1, a first subject could be treated at the next dose level.
If 2 or more of the 6 subjects experienced a DLT during Cycle 1 the dose escalation was stopped.
The highest dose level at which < 2 of 6 subjects experienced a DLT is defined as the MTD.
- Qualitative and Quantitative Toxicities of BT062 [ Time Frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months) ]
Qualitative and quantitative toxicities assessed by incidence of adverse events and by clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results.
The incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs).
- Multi-dose Pharmacokinetics Properties of BT062 - Cmax [ Time Frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months). ]
Multi-dose Pharmacokinetics properties of BT062 after intravenous (IV) Administration of escalating doses of BT062 as assessed by measuring intact BT062 conjugate.
Please note that not all subjects reached Cycle 4 due to early termination . A lower number of samples could be analyzed for Cycle 4.
- Anti-tumor Activity of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma by Number of Participants With Objective Response(ORR) and/or Clinial Benefit(CBR) Based on the International Myeloma Working Group Uniform Response Criteria [ Time Frame: On day 1 of each treatment cycle (on a monthly basis) starting with first study drug administration until Close Out visit (average 3.84 months). ]sCR:CR+normal FLC+absence of clonal cells in BM; CR:Negative immunofixation,disappearance of soft tissue plasmacytomas +≤5% plasma cells in BM+normal FLC; VGPR:M-protein detectable by immunofixation,not on electrophoresis or 90% or greater reduction in serum M-protein+urine M-protein level <100mg per 24h,>90% decrease in the difference between involved/uninvolved FLC; PR:≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h or ≥50% decrease in the difference between involved/uninvolved FLC or ≥50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%, ≥50% size reduction of soft tissue plasmacytomas; MR:25%-49% reduction of serum M-protein+reduction in 24h urinary M-protein by 50-89%(still >200 mg/24h),25-49% soft tissue plasmacytomas size reduction,no increase in size or number of lytic bone lesions; SD:no response or PD ORR: %of subjects with MR+PR+VGPR+CR+sCR CBR:ORR + %of subjects with SD.
- Time to Progression (TTP), Progression Free Survival (PFS) and Overall Survival (OS) [ Time Frame: Starting with first study drug administration until death or 3 years from first study treatment. ]
Requires any one or more of the following:
Increase of ≥ 25% from baseline in
- Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL) (increases of ≥ 1 g/dL are sufficient to define relapse if starting M-component is ≥ 5 g/dL).
- Urine M-component and/or (the absolute increase must be ≥ 200mg/24h).
Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL.
Bone marrow plasma cell percentage: the absolute % must be ≥ 10% (relapse form CR as a 5% cutoff instead of 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 hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/l) that can be attributed solely to the plasma cell proliferative disorder.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01001442
|United States, Georgia|
|Emory University Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|The University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|The Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|Study Director:||Kenneth C. Anderson, MD||Dana-Farber Cancer Institute|