Oral TP-3654 for Myelofibrosis
Recruiting in Palo Alto (17 mi)
+58 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Sumitomo Dainippon Pharma Oncology, Inc
Must be taking: Ruxolitinib, Momelotinib
Must not be taking: Systemic steroids
Disqualifiers: Chronic liver disease, Heart failure, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary MF.
Do I need to stop my current medications to join the trial?
The trial does not specify that you must stop all current medications, but certain treatments like systemic antineoplastic therapy or experimental therapies must be stopped at least 2 weeks or 5 half-lives before starting the trial. If you are on a JAK inhibitor like ruxolitinib, you may need to taper off over at least 1 week. Hydroxyurea or anagrelide can be taken up to 24 hours before starting the trial.
What makes the drug TP-3654 unique for treating myelofibrosis?
TP-3654, also known as Nuvisertib, is unique because it is an oral treatment for myelofibrosis, which may offer a different mechanism of action compared to existing JAK2 inhibitors like fedratinib and ruxolitinib. While the specific details of TP-3654's action in myelofibrosis are not provided, its development suggests it may target pathways not addressed by current standard treatments.12345
Eligibility Criteria
This trial is for adults with primary or secondary myelofibrosis, a type of bone marrow cancer. They must have tried and failed JAK inhibitor treatment or be ineligible for it. Participants need to have certain blood counts, organ function within specific limits, and a life expectancy of at least 3 months. They can't join if they've had recent surgeries or other treatments that could interfere with the study.Inclusion Criteria
I agree to give bone marrow samples at the start and every 6 months during the study.
My spleen is enlarged, confirmed by a doctor's exam or imaging tests.
- Life expectancy ≥ 3 months
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Exclusion Criteria
My electrolyte levels are stable or can be corrected.
I haven't had cancer treatment or experimental therapy in the last 14 days or 5 half-lives, whichever is longer.
I have had my spleen removed or received spleen radiation in the last 6 months.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive nuvisertib (TP-3654) in various combinations depending on the arm, with dose-escalation to assess safety, tolerability, pharmacokinetics, and pharmacodynamics
24 weeks
Regular visits for dose-escalation and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of spleen volume reduction and symptom score improvement
12 weeks
Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks thereafter during treatment
Long-term follow-up
Participants are monitored for overall survival and long-term safety outcomes
From start of treatment to end of study
Treatment Details
Interventions
- TP-3654 (Other)
Trial OverviewThe trial is testing TP-3654, an oral medication for myelofibrosis patients who are at intermediate or high risk. It's in early stages (Phase 1/2) to see how safe it is and how the body responds to different doses. Patients will also undergo regular bone marrow biopsies to monitor effects.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Arm 3: nuvisertib (TP-3654) in combination with momelotinibExperimental Treatment2 Interventions
Group II: Arm 2: nuvisertib (TP-3654) added on to ruxolitinibExperimental Treatment2 Interventions
Group III: Arm 1: nuvisertib (TP-3654)Experimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory UniversityAtlanta, GA
University of ChicagoChicago, IL
Washington University of MedicineSaint Louis, MO
Memorial Sloan Kettering Cancer CenterNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Sumitomo Dainippon Pharma Oncology, IncLead Sponsor
Sumitomo Pharma Oncology, Inc.Lead Sponsor
Sumitomo Pharma America, Inc.Lead Sponsor
References
Ruxolitinib for the treatment of primary myelofibrosis. [2021]The pharmacology, pharmacokinetics, pharmacogenomics, clinical efficacy, and safety profile of ruxolitinib for the treatment of primary myelofibrosis are reviewed.
Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase-2 (JAK2), in patients with myelofibrosis and low pretreatment platelet counts. [2022]Fedratinib, an oral Janus kinase-2 (JAK2) inhibitor, is approved for patients with myelofibrosis (MF) and platelet counts ≥50 × 109 /l, based on outcomes from the phase 3, placebo-controlled JAKARTA trial in JAK-inhibitor-naïve MF, and the phase 2, single-arm JAKARTA2 trial in patients previously treated with ruxolitinib. We evaluated the efficacy and safety of fedratinib 400 mg/day in patients with baseline platelet counts 50 to <100 × 109 /l ("Low-Platelets" cohorts), including 14/96 patients (15%) in JAKARTA and 33/97 (34%) in JAKARTA2. At 24 weeks, spleen response rates were not significantly different between the Low-Platelets cohort and patients with baseline platelet counts ≥100 × 109 /l ("High-Platelets" cohort), in JAKARTA (36% vs. 49%, respectively; p = 0.37) or JAKARTA2 (36% vs. 28%; p = 0.41). Symptom response rates were also not statistically different between the Low- and High-Platelets cohorts. Fedratinib was generally well-tolerated in both platelet-count cohorts. New or worsening thrombocytopaenia was more frequent in the Low-Platelets (44%) versus the High-Platelets (9%) cohort, but no serious thrombocytopaenia events occurred. Thrombocytopaenia was typically managed with dose modifications; only 3/48 Low-Platelets patients discontinued fedratinib due to thrombocytopaenia. These data indicate that fedratinib 400 mg/day is safe and effective in patients with MF and low pretreatment platelet counts, and no initial fedratinib dose adjustment is required for these patients.
Patient characteristics and outcomes after ruxolitinib discontinuation in patients with myelofibrosis. [2021]Background: This retrospective analysis evaluates morbidities, outcomes and associated risk factors in patients with myelofibrosis (MF) after ruxolitinib discontinuation, using Truven Health Analytics MarketScan (TR), Optum integrated virtual electronic health records and claims databases (OP), and Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (SM).Methods: A total of 290 patients with MF between 2006 and 2015 (using ICD-9 and ICD-O-3 codes), who were treated with and discontinued ruxolitinib were identified. Only patients with ≥90 days of medical history prior to index diagnosis (TR + OP) and Part A, B, and D enrollment at the time of index diagnosis (SM) were included. Morbidities were assessed during the 30-day period each following ruxolitinib initiation, prior to and post ruxolitinib discontinuation. Cumulative incidence of cytopenias and efficacy outcomes were evaluated from baseline.Results: Median age of patients was 68 years, with equal proportion of either gender. Median time to ruxolitinib discontinuation was 284 days and median follow-up after discontinuation was 70.9 days. The majority of patients were diagnosed with anemia and >30% of the patients received RBC transfusions during 30-day period prior to and the 30-day period post ruxolitinib discontinuation. After ruxolitinib discontinuation, half of the patients developed cytopenias. The median treatment progression-free survival, and overall survival after ruxolitinib discontinuation were 6.0 (4.4, 8.3) months and 11.1 (8.4, 14.5) months, respectively. Age at ruxolitinib discontinuation (HR [95% CI] = 2.071 [1.320, 3.248]), Charlson Comorbidity Index score (HR [95% CI] = 1.172 [1.093, 1.257]) and gender (HR [95% CI] = 1.620 [1.108, 2.369]) increased the risk of treatment progression (start of the subsequent treatment regimen) or death.Conclusion: Results from this large, retrospective, US population-based outcome analysis of MF patients show an increase in morbidity burden and identifies the risk factors of survival outcomes among real-world patients who have discontinued ruxolitinib.
Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. [2022]Fedratinib, an oral Janus kinase-2 (JAK2) inhibitor, reduces splenomegaly and improves symptom burden in patients with myelofibrosis. Regulatory approval of fedratinib 400-mg daily was based on results of an updated analysis of the pivotal phase III, placebo-controlled JAKARTA trial in patients with JAK-inhibitor-naïve myelofibrosis. At week 24, spleen volume response rate was 47% and symptom response rate was 40% with fedratinib 400 mg, versus 1% and 9% respectively, with placebo. Common adverse events were diarrhoea, nausea, anaemia, and vomiting. No Wernicke encephalopathy occurred in patients receiving fedratinib 400 mg/day. These updated data support use of first-line fedratinib in patients with myelofibrosis.
Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. [2022]Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin