NCT02493530

TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea

A Phase 1 Dose Escalation and Expansion Study of TGR-1202 + Ruxolitinib in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (PPV-MF), Post-Essential Thrombocythemia MF (PET-MF), MDS/MPN, or Polycythemia Vera Resistant to Hydroxyurea

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• Myelofibrosis
• Polycythemia Vera

Interventions

Type	Name	Description
DRUG	TGR-1202	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 highest tolerated 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. TGR-1202 will be administered at or below the recommended dose established in Stage 1. Expansion will commence after proper combination doses of both agents is established.
DRUG	ruxolitinib

Timeline

• Start date: 2015-07-01
• Primary completion: 2023-03-21
• Completion: 2024-05-01
• First posted: 2015-07-09
• Last updated: 2024-06-27

Locations

5 sites across 1 country: United States