A Study of Oral TP-3654 in Patients With Myelofibrosis
- Conditions
- Myelofibrosis
- Interventions
- Registration Number
- NCT04176198
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of TP-3654 in patients with intermediate or high-risk primary or secondary MF.
- Detailed Description
Arm 1 will enroll patients who have been previously treated and failed on a JAK inhibitor or ineligible to receive treatment with a JAK inhibitor.
Arm 2 will enroll patients who are on a stable dose of ruxolitinib, but who have either lost response or had a suboptimal or plateau in response.
Arm 3 will enroll patients who have been previously treated on JAK inhibitor (except momelotinib) that was complicated by anemia, thrombocytopenia or hematoma.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: nuvisertib (TP-3654) Nusivertib - Arm 3: nuvisertib (TP-3654) in combination with momelotinib Nusivertib - Arm 3: nuvisertib (TP-3654) in combination with momelotinib Momelotinib - Arm 2: nuvisertib (TP-3654) added on to ruxolitinib Nusivertib - Arm 2: nuvisertib (TP-3654) added on to ruxolitinib Ruxolitinib -
- Primary Outcome Measures
Name Time Method Determine the incidence of dose-limiting toxicities (DLTs) 28 days Number of participants with DLTs
Determine the incidence of treatment emergent adverse events From start of treatment to end of study Number of participants with Treatment Emergent Adverse Events and Serious Adverse Events
Assess patients for any evidence of preliminary activity by determining the number of patients with ≥ 35% spleen volume reduction (SVR35) From start of treatment to end of study Number of participants with ≥ 35% spleen volume reduction (SVR35)
- Secondary Outcome Measures
Name Time Method Number of participants achieving objective response by IWG-MRT response criteria From start of treatment to end of study Number of participants achieving complete remission, partial remission, clinical improvement, progressive disease and stable disease.
Number of participants who have ≥ 25% spleen volume reduction Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks therafter during treatment. Number of participants who have ≥ 25% spleen volume reduction compared to baseline
Number of participants with ≥ 50% improvement in total symptom score (TSS50) at week 24 24 weeks Number of participants who have ≥ 50% total symptom score reduction by MFSAF compared to baseline after 24 weeks of treatment.
Determine the change in Patient Global Impression of Change (PGIC) at week 24 through end of study. After 24 weeks of treatment to end of study Change in PGIC score
Determine the incidence of QT interval changes 25 hours Changes in QT interval and heart rhythm
Establish the half-life (t½) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib 24 hours The estimate of time for the nuvisertib concentration or amount to be reduced by half
Establish the Area under the plasma concentration versus time curve (AUC) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib 24 hours The amount of drug exposure over 24 hours period after administration
Establish the Peak Plasma Concentration (Cmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib 24 hours The maximum nuvisertib concentration after administration
Establish the Time of Maximum concentration observed (tmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib 24 hours The time to reach maximum nuvisertib concentration
Trial Locations
- Locations (61)
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Mie University Hospital
🇯🇵Tsu, Japan
University of Alabama
🇺🇸Birmingham, Alabama, United States
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Hoag Family Cancer Institute
🇺🇸Newport Beach, California, United States
Blood Cancer Center
🇺🇸Denver, Colorado, United States
University of Florida Health Shands Cancer Hospital
🇺🇸Gainesville, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University of Medicine
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Montefiore Cancer Center
🇺🇸Bronx, New York, United States
Centre Hospitalier Universitaire D'Amiens
🇫🇷Amiens, France
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Weill Cornell Medical Center
🇺🇸New York, New York, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Tri-Star Centennial Medical Center
🇺🇸Nashville, Tennessee, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
University of Washington - Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Eastern Health Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Monash University
🇦🇺Clayton, Victoria, Australia
Icon Cancer Centre (Ashford Cancer Centre Research)
🇦🇺Adelaide, Australia
University Hospitals Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
ZNA Cadix
🇧🇪Antwerp, Belgium
ZNA Middelheim
🇧🇪Antwerp, Belgium
University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Hospitalier Universitaire (CHU) de Nice - Hopital de l'Archet
🇫🇷Nice, France
Institut de cancerologie du Gard
🇫🇷Nimes, France
Hospital Saint Louis
🇫🇷Paris, France
Institut Gustave Roussy
🇫🇷Villejuif, France
IRCCS istituto Romagnolo per lo studio dei tumori "Dino Amadori"
🇮🇹Meldola, Italy
IRCCS Azienda Ospedaliero -Universitaria Di Bologna - Dipartimento Malattie Oncologiche ed Ematologiche - UO Ematologia
🇮🇹Bologna, Italy
ASST - Spedali Civili di Brescia
🇮🇹Brescia, Italy
Aichi Medical University Hospital
🇯🇵Aichi, Japan
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Azienda Ospedaliera Universitaria Citta' Della Salute E della Scienza di Torino
🇮🇹Torino, Italy
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
University of Miyazaki Hospital
🇯🇵Miyazaki, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Saitama Medical Center
🇯🇵Saitama, Japan
Tohoku University Hospital
🇯🇵Sendai, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
United Lincolnshire Hospitals NHS Trust - Pilgrim Hospital
🇬🇧Lincoln, United Kingdom
University College London Hospital's NHS foundation Trust
🇬🇧London, United Kingdom