Safety and Preliminary Efficacy Study of the Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma
- To evaluate the safety and tolerability of escalating doses of an intravenous (i.v.) infusion of PAT-SM6 in subjects with relapsed or refractory multiple myeloma.
- To evaluate the efficacy and pharmacodynamics by analysis of serum and urine M protein, serum free light chains (FLC) κFLC and λFLC, total immunoglobulins, β2-microglobulin, C-reactive protein (CRP), exploratory biomarkers and anti-PAT-SM6 antibodies.
- To evaluate the duration of response and the progression free survival.
Biological: Anti-GRP78 monoclonal IgM antibody PAT-SM6
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open-label, Single-centre, Phase I, Multi-dose Escalating Study to Investigate the Safety and Preliminary Efficacy of an i.v. Infusion of the Anti-GRP78 Monoclonal IgM Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma|
- Overall frequency of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events (SAEs) and treatment limiting adverse events) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
- Serum concentrations of PAT-SM6 [ Time Frame: 11 days ] [ Designated as safety issue: No ]
- Pharmacodynamics [ Time Frame: 40 days ] [ Designated as safety issue: No ]
- Efficacy [ Time Frame: 40 days ] [ Designated as safety issue: No ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: Antibody treatment
Intravenous infusion of the anti-GRP78 monoclonal IgM antibody PAT-SM6 group 1: 0.3mg/kg Group 2: 1.0mg/kg Group 3: 3mg/kg Group 4: 6mg/kg
|Biological: Anti-GRP78 monoclonal IgM antibody PAT-SM6|
Open-label, single-centre, dose escalation phase I study designed to investigate the safety and tolerability of intravenous (i.v.) infusions of PAT-SM6 administered over 90 minutes.
A screening examination will be performed within 14 days prior to dosing. Eligible subjects will receive 4 doses of PAT-SM6 (cycle 1: Day 1 and Day 3, cycle 2: Day 8 and Day 10). Subjects will be hospitalised for at least 48 hours after each dose administration (i.e. from Day 1 to Day 5 in cycle 1 and from Day 8 to Day 12 in cycle 2). During hospitalisation subjects will be under constant surveillance. Subjects will return for ambulatory visits on Days 15, 22, 29 and 36 for safety, pharmacokinetic (PK) and pharmacodynamic (PD) assessments.
Serological staging will be performed at baseline, on Day 29 (+/- 2 days) and Day 36 (+/-2 days). Response will be assigned by the International Myeloma Working Group (IMWG) uniform response criteria for multiple myeloma. Complete response (CR) will be confirmed by bone marrow aspiration; CT scans or other radiograph are only intended when clinical symptoms are suspicious for progressing disease or otherwise clinically indicated.
If a subject shows an at least partial response (PR) on Day 29 or Day 36 (4 doses) the sponsor discusses with the Data Safety Monitoring Board (DSMB) to give an additional 2 doses (therefore the maximal number of doses for each subject is 6 doses) and a further staging will be performed 14 and 21 days after the last dose administration.
A completion visit will be performed 4 days after the last serological staging (e.g. after cycle 2 on Day 40).
Four dose groups (cohorts) are planned: 0.3 mg/kg followed by doses of 1 mg/kg, 3 mg/kg and 6 mg/kg. Subjects will be enrolled in a strict sequential order.
Individual safety results obtained until Day 5 will be evaluated by the investigator and the sponsor before the next subject of the same dose group will be treated. After completion of all 3 subjects of a dose group, safety results of all subjects obtained until Day 15 will be reviewed by the DSMB and a decision for dose escalation will be made. Interim doses can be administered if the increase is thought to be too high.
Subjects who show definite signs of progressive disease including hypercalcemia, new osteolytic lesions or new soft tissue plasmocytoma will be withdrawn from the study at any time.
In case dose limited toxicity (DLT) was seen in a subject, further dosing of subjects in the same dose group will be discussed with the DSMB, in case of a second DLT in the same dose group dose escalation will be stopped and the study will be continued at the next lower intermediate dose level or the previous tested dose will be regarded as the maximum tolerated dose (MTD). The MTD is defined as the dose level below the dose inducing a DLT in 2 subjects within one dose level.
|Contact: Leo Rasche, MD||+49 (0) 931 201 ext email@example.com|
|Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II||Recruiting|
|Wuerzburg, Germany, 97080|
|Contact: Leo Rasche, MD firstname.lastname@example.org|
|Sub-Investigator: Leo Rasche, MD|
|Principal Investigator:||Max Top, MD||Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Zentrum für Innere Medizin,|