TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea
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|ClinicalTrials.gov Identifier: NCT02493530|
Recruitment Status : Recruiting
First Posted : July 9, 2015
Last Update Posted : October 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis Polycythemia Vera||Drug: TGR-1202 Drug: ruxolitinib||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||112 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||TGR-1202 + Ruxolitinib in Subjects With Myelofibrosis, MDS/MPN, or Polycythemia Vera Resistant to Hydroxyurea|
|Study Start Date :||July 2015|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||December 2019|
Experimental: Escalation and expansion
TGR1202 and Ruxolitinib combination
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.
Other Name: Jakafi
- Safety of TGR1202 in combination with ruxolitinib [ Time Frame: </=12 months ]All patients who have received at least one dose of TGR-1202 will be included in the safety population. All clinical safety data (vital signs, routine laboratory tests, and adverse events) will be tabulated and listed. The safety and tolerability of TGR-1202 and ruxolitinib will be evaluated by means of drug-related dose limiting toxicity, adverse event (AE) reports, physical examinations and laboratory safety evaluations.
- 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.
- TGR-1202's effects plasma cytokine levels when added to ruxolitinib [ Time Frame: 0-16 weeks ]
- JAK2V617F allele burden [ Time Frame: 0-16 weeks ]Measurement of JAK2V617F allele burden by PCR
- Mutations found on next generation sequencing (NGS) correlated with response [ Time Frame: EOT 1 year ]
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): NCT02493530
|Contact: VICC Clinical Trials Information Program||800-811-8480|
|United States, Arizona|
|Mayo Clinic - Arizona||Recruiting|
|Phoenix, Arizona, United States, 85054|
|Contact: Clinical Trials Office 855-776-0015|
|Principal Investigator: Ruben Mesa, MD|
|United States, Colorado|
|University of Colorado Cancer Center||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Clinical Trials Office 720-848-0018|
|Principal Investigator: Daniel A Pollyea, MD, MS|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Clinical Trials Office 800-811-8480|
|Principal Investigator: Michael R Savona, MD|
|United States, Wisconsin|
|Medical College of Wisconsin||Recruiting|
|Milwaukee, Wisconsin, United States, 53226|
|Contact: Clinical Trials Office 414-805-1118|
|Principal Investigator: Laura C. Michaelis, MD|
|Principal Investigator:||Michael Savona, MD||Vanderbilt-Ingram Cancer Center|