Efficacy and Safety of SNX-5422 Added to an Established Dose of Ibrutinib in CLL
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-label Study of SNX‑5422 Added to Ibrutinib in Chronic Lymphocytic Leukemia Subjects With Residual Disease|
- Efficacy of the combination of SNX-5422 and ibrutinib [ Time Frame: 6 months ] [ Designated as safety issue: No ]Proportion of subjects obtaining a complete response at the end of 6 SNX-5422 treatment cycles
- Number of subjects reporting adverse events [ Time Frame: Day 28 of each 4 week cycle from randomization up to 52 weeks ] [ Designated as safety issue: Yes ]Frequency and severity of adverse events
- Complete response at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]Proportion of subjects obtaining a complete response at the end of 6 SNX-5422 treatment cycles
- Improved Clinical Status [ Time Frame: 6 months ] [ Designated as safety issue: No ]Proportion of subjects obtaining improvement in clinical status (i.e., Stable Disease becoming Partial Response) at the end of 6 SNX-5422 treatment cycles
- Progression free survival of patients receiving ibrutinib plus SNX-5422 [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]Elapsed time for each subject from randomization to continued survival up to 52 weeks
- BTK Mutation Level [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]Change from baseline in percent of CLL cells with Bruton's Tyrosine Kinase mutations at the end of 6 and 12 treatment cycles
|Study Start Date:||December 2016|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
Experimental: SNX-5422 plus ibrutinib
Open-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle. Subjects will repeat the 28-day schedule for 2 cycles after a CR or until the cancer progresses or the subject is unable to tolerate the therapy
Drug: SNX-5422 plus ibrutinib
SNX-5422 capsule(s) dosed every other day for 21 days out of a 28-day treatment cycle to a total dose of 56 mg/m2 SNX-5422. Subjects will self-administer daily oral ibrutinib in the afternoon at least 8 hours apart from SNX-5422 for 28 days of each cycle.
Other Name: Imbruvica
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation. Significant advances have been made in the therapy, notably with the introduction of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib.
While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. In addition, although remissions are durable in many patients, very few patients achieve a complete response (CR), and minimal residual disease (MRD) negativity on single agent ibrutinib has not been reported. Since it is known that for chemoimmunotherapy as well as targeted therapies such as venetoclax that attainment of a CR is associated with longer progression free survival (PFS), it is likely that deepening responses associated with ibrutinib will result in more durable remissions.
Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, the other is through a variety of mutations in the immediate downstream target of BTK, PLCγ2. SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will provide clinical response in subjects who have residual disease, but have not progressed on ibrutinib after 18 months of monotherapy.
Subjects will receive SNX‑5422 (56 mg/m2) in the morning once every other day for 21 days (11 doses), followed by a 7‑day drug‑free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon
Please refer to this study by its ClinicalTrials.gov identifier: NCT02973399
|Contact: Eric Orlemans, PhDfirstname.lastname@example.org|
|United States, Ohio|
|Wexner Medical Center, Ohio State University||Not yet recruiting|
|Columbus, Ohio, United States, 43210|
|Principal Investigator: Jennifer A Woyach, MD|