SST0001 (Roneparstat) in Advanced Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT01764880|
Recruitment Status : Completed
First Posted : January 10, 2013
Last Update Posted : October 23, 2017
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: SST0001 (Roneparstat)||Phase 1|
Multicenter, open label, uncontrolled Phase I First In Man trial in advanced refractory multiple myeloma, to determine the Maximum Tolerated Dose (MTD) of SST0001 given subcutaneously (sc) once daily for 5 or 10 days, in a cycle of 28 days. A starting dose of 25 mg (flat dose) is given once daily for 5 days (from Day 1 to Day 5). In the subsequent cohort 25 mg are administered once daily for 10 days (from Day 1 to 5 and from Day 8 to 12). Dose escalation with SST0001 administered for 10 days is performed in subsequent cohorts, depending on toxicities observed.
Indirect pharmacokinetics based on Activated Partial Thromboplastin Time (aPTT) modifications in all patients (minimum of 3 patients in each cohort) during the first cycle of treatment and direct SST0001 concentrations measurements.
Pharmacodynamics in all patients during the first cycle of treatment, based on modifications of coagulation parameters.
During the study any hints of anti-tumor activity will also be evaluated based on use of surrogate parameters (monoclonal serum and urine protein modifications).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Finding Study Assessing Safety and Tolerability of SST0001 in Advanced Multiple Myeloma.|
|Study Start Date :||November 2012|
|Actual Primary Completion Date :||November 2016|
|Actual Study Completion Date :||November 2016|
Experimental: SST0001 (Roneparstat)
SST0001 once daily for 5 or 10 days in a cycle of 28 days. Starting dose 25 mg, to be escalated in subsequent cohorts.
Duration of treatment depending on toxicities observed or until documentation of disease progression or other discontinuation criteria are met.
Drug: SST0001 (Roneparstat)
SST0001 once daily for 5 or 10 days in a cycle of 28 days.
- Maximum tolerated dose (MTD). [ Time Frame: 28 days of first cycle of therapy. ]Maximum tolerated dose (MTD) (based upon first cycle study drug related dose limiting toxicities [DLTs]) of SST0001 given subcutaneously over repeated administration during each treatment cycle. MTD definition: ≥ 2/6 patients with a DLT at the first cycle (28 days).
- Adverse events, physical examination and laboratory tests. [ Time Frame: 28 days of each cycle of therapy. ]Number of patients with adverse events, number of patients with abnormalities at physical examination and laboratory tests (hematology and biochemistry) as a measure of safety and local tolerability of SST0001. Safety assessments and severity of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
- Maximum plasma concentration (Cmax) [ Time Frame: 28 days of first cycle of therapy. ]Blood pharmacokinetics of SST0001 using Activated Partial Thromboplastin Time (aPTT)as indirect measurement of SST0001 equivalent plasma concentrations.
- Time to achieve Cmax (Tmax) [ Time Frame: 28 days of first cycle of therapy. ]
- Area under the concentration curve from administration to the last observed concentration time (AUClast) [ Time Frame: 28 days of first cycle of therapy. ]
- Half-life (T1/2) [ Time Frame: 28 days of first cycle of therapy. ]
- aPTT (Activated Partial Thromboplastin Time) [ Time Frame: 28 days of first cycle of therapy. ]Pharmacodynamics of SST0001 in terms of effects on coagulation profile (aPTT, seconds).
- TT (Thrombin Time) [ Time Frame: 28 days of first cycle of therapy. ]Pharmacodynamics of SST0001 in terms of effects on coagulation profile (TT, seconds).
- INR (International Normalized Ratio) [ Time Frame: 28 days of first cycle of therapy. ]Pharmacodynamics of SST0001 in terms of effects on coagulation profile (INR).
- Tumor response. [ Time Frame: 28 days of each cycle of therapy. ]
Antitumor activity through the use of surrogate parameters (monoclonal serum and urine protein modifications), by means of serum and urine protein electrophoresis, immunoelectrophoresis and immunofixation, Serum Free Light Chain (FLC) Ratio and/or 24-h Bence-Jones urine protein.
M-protein (g/dL), Bence-Jones protein (g/24h), kappa FLC (mg/dL) and lambda FLC (mg/dL) will be assessed at each cycle of therapy. Responses will be evaluated according to International Myeloma Working Group (IMWG) Guidelines.
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): NCT01764880
|Würzburg, Germany, 97080|
|Division of Hematology, Chaim Sheba Medical Center|
|Tel Hashomer, Israel|
|U.O. Ematologia con Trapianto, Dipartimento dell'Emergenza e dei Trapianti di Organi|
|Bari, Italy, 70124|
|USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII|
|Bergamo, Italy, 24127|
|S.C. Ematologia, ASO S. Croce e Carle - Cuneo|
|Cuneo, Italy, 12100|
|Principal Investigator:||Alessandro Rambaldi, MD||USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy|
|Principal Investigator:||Arnon Nagler, MD||Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel|
|Principal Investigator:||Manik Chatterjee, MD||Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik II (ZIM), Würzburg, Germany|