Clinical Trial: TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: TGR-1202 + Ruxolitinib in Subjects With Myelofibrosis, MDS/MPN, or Polycythemia Vera Resistant to Hydroxyurea
Brief Summary: This is a Phase 1, open-label, study of TGR-1202, a PI3K delta inhibitor, administered together with ruxolitinib in patients with myeloproliferative neoplasms (specifically: polycythemia vera, primary myelofibrosis, PPV-MF or PET-MF) and MDS/MPN.
Detailed Summary:
The escalation will include 2 initial sequential stages. Stage 1 will include myelofibrosis or hydroxyurea-resistant/refractory PV patients already taking therapeutic levels of ruxolitinib, but who are not achieving maximal response at the highest tolerated dose of ruxolitinib as discussed among investigators. Only TGR-1202 will be escalated in a modified 3+3 dose escalation algorithm to determine the MTD of TGR-1202 to be given with any given dose of ruxolitinib.
Stage 2 will include myelofibrosis or hydroxyurea-resistant/refractory PV patients who have never been on JAK-STAT inhibitory agents, and includes simultaneously initiation of both ruxolitinib and TGR-1202. In Stage 2, JAK Inhibitor naïve patients will receive TGR-1202 at the recommended dose established in Cohort 1, and ruxolitinib. As patients in Stage 1 will be on ruxolitinib at different doses, dose levels in Stage 2 will expand to meet requirements for safety analysis.
Sponsor: Vanderbilt-Ingram Cancer Center
Current Primary Outcome: Safety of TGR1202 in combination with ruxolitinib [ Time Frame: </=12 months ]
Original Primary Outcome: Safety of TGR1202 in combination with ruxolitinib [ Time Frame: Duration of the study ]
Current Secondary Outcome:
- Overall response [ Time Frame: EOT - 12 months ]Number of patients in each response category, polycythemia IWG response criteria, IWG-MRT response criteria, IWG MDS/MPN response criteria summarized as follows for target lesion criteria (see IWG for additional details): complete response (CR), normalization of bone marrow, peripheral counts, spleen size, and symptoms; partial response (PR); Hematologic improvement (HI), or progressive disease (PD). Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>HI>SD>PD.
- Total symptom score (MPN-TSS) [ Time Frame: 16 weeks of therapy ]The myeloproliferative neoplasm - total symptoms score (MPN-TSS) is a validated tool in measurement in symptoms for patients with these diseases and we will measure patient reported outcomes with this validated tool
- Blood levels of TGR1202 in combination with ruxolitinib (Pharmacokinetics) [ Time Frame: 30 days ]The PK parameters (including AUC (0-∞), AUC (0- τ), Cmax, tmax, λz, and t½) of TGR-1202 and ruxolitinib following will be assessed by analysis of TGR-1202 plasma concentrations during the dose escalation phase of the study.
Original Secondary Outcome:
- Overall response [ Time Frame: EOT - 12 months ]Number of patients in each response category, polycythemia IWG response criteria, IWG-MRT response criteria, IWG MDS/MPN response criteria summarized as follows for target lesion criteria (see IWG for additional details): complete response (CR), normalization of bone marrow, peripheral counts, spleen size, and symptoms; partial response (PR); Hematologic improvement (HI), or progressive disease (PD). Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>HI>SD>PD.
- Total symptom score (MPN-TSS) [ Time Frame: 16 weeks of therapy ]The PK parameters (including AUC (0-∞), AUC (0- τ), Cmax, tmax, λz, and t½) of TGR-1202 and ruxolitinib following will be assessed by analysis of TGR-1202 plasma concentrations during the dose escalation phase of the study.
- Pharmacokinetics of TGR1202 in combination with ruxolitinib [ Time Frame: 30 days ]The PK parameters (including AUC (0-∞), AUC (0- τ), Cmax, tmax, λz, and t½) of TGR-1202 and ruxolitinib following will be assessed by analysis of TGR-1202 plasma concentrations during the dose escalation phase of the study.
Information By: Vanderbilt-Ingram Cancer Center
Dates:
Date Received: July 1, 2015
Date Started: July 2015
Date Completion: July 2019
Last Updated: November 19, 2016
Last Verified: November 2016