Safety, PK, PD, and Antitumor Activity of SNS-062 in B Lymphoid Cancers
|Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Lymphoplasmacytoid Lymphoma Mantle-Cell Lymphoma Waldenstrom Macroglobulinemia||Drug: SNS-062||Phase 1 Phase 2|
|Study Design:||Intervention Model: Sequential Assignment
Intervention Model Description:
Phase 1b will evaluate the safety and pharmacology of a range of SNS-062 dose levels administered to the subjects. Based on the pattern of dose limiting toxicities observed in the first cycle (4 weeks), escalation will proceed to define a maximum tolerated dose (MTD) and/or a recommended dose (RD). The Phase 2 portion of the study provides cohort expansion to further explore the clinical activity, safety and pharmacology of SNS-062 monotherapy.Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor, SNS-062, in Patients With B-Lymphoid Malignancies|
- Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b) [ Time Frame: Up to approximately 21 months ]To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD)within the tested SNS-062 dose range. The MTD is the highest tested dose level at which ≥6 subjects have been treated and which is associated with a Cycle 1 dose limiting toxicity (DLT) in <33% of the subjects. The RD may be the MTD or may be a lower dose.
- Objective Response Rate (ORR) (Phase 2) [ Time Frame: Approximately 24 months ]
Phase 2 portion of study measuring ORR and corresponding 95% confidence intervals by cohort. ORR will be defined by disease subtype as the proportion of subjects who achieve CLL/SLL: a CR, CRi, or PR.
MCL: a CR or PR. LPL/WM: a CR, VGPR, PR, or MR.
- Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings [ Time Frame: Up to approximately 24 months ]Type, severity, timing of onset, duration, and relationship to study drug of any TEAEs or abnormalities of laboratory tests, SAEs, DLTs, or AEs leading to study discontinuation.
- Characterization of Pharmacokinetics (AUC) [ Time Frame: Up to approximately 24 months ]Area Under the Curve (AUC)
- Characterization of Pharmacokinetics (Cmax) [ Time Frame: Up to approximately 24 months ]Maximum Plasma Concentration (Cmax)
|Actual Study Start Date:||April 28, 2017|
|Estimated Study Completion Date:||June 30, 2021|
|Estimated Primary Completion Date:||September 30, 2018 (Final data collection date for primary outcome measure)|
Experimental: Dose escalating cohorts of SNS-062
Sequential groups, 25, 50, 100, 200, 300, 400 and 500 mg twice daily on to determine maximum tolerated dose and recommended dose (RD) in the treatment of various hematological cancers followed by expansion of the recommended dose cohort in Phase 2 of the study treating hematological cancers.
SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.
Phase 1b (Dose Escalation) This portion of the study will evaluate the safety and pharmacology of a range of SNS-062 dose levels administered to subjects with previously treated B-lymphoid malignancies, including: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), and mantle cell lymphoma (MCL).
All subjects will self-administer SNS-062 orally BID. The dose-limiting toxicity (DLT) window will be 4 weeks (1 cycle in length). Assessments after the DLT window will be performed in 4-week cycles. Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of SNS-062 using a standard 3+3 dose-escalation design.
Based on the pattern of dose-limiting toxicities (DLTs) observed in the first cycle (4 weeks), escalation will proceed to define a maximum tolerated dose (MTD) and/or a recommended dose (RD) that may be the MTD or a lower dose. An additional 6 subjects may be accrued at the MTD or the RD to confirm SNS-062 safety and pharmacology as a prelude to further clinical evaluation. Assessments regarding DLTs and dose escalation will be performed by a SRC comprising, but not limited to, the principal investigators, the medical monitor and the study sponsor drug safety representative.
Phase 2 (Cohort Expansion) This portion of the study provides cohort expansion to further explore the clinical activity, safety, and pharmacology of SNS-062 monotherapy. Accrual will be by enrollment into each disease and mutation specific cohort. Subjects will self-administer SNS-062 orally at the RD of SNS-062 identified in the Phase 1b portion of the study. Study personnel will meet regularly to assess the efficacy and safety for each cohort.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03037645
|Contact: Meisa Propstemail@example.com|
|United States, California|
|University of California Irvine Medical Center||Recruiting|
|Orange, California, United States, 92868-3201|
|Contact: General Contact 877-827-8839 firstname.lastname@example.org|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Mike Rocchio 617-632-5221 MichaelJ_Rocchio@dfci.harvard.edu|
|United States, New York|
|Weill Cornell Medicine||Recruiting|
|New York, New York, United States, 10065|
|Contact: Carol Bivins 713-794-4660 email@example.com|
|United States, Ohio|
|The Ohio State University||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Beth Wiley 614-293-3660 firstname.lastname@example.org|
|United States, Texas|
|MD Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Study Director:||Renee Ward, MD, PhD||Sunesis Pharmaceuticals|