Oral TP-3654 for Myelofibrosis
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Sumitomo Dainippon Pharma Oncology, Inc
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.
Is the drug TP-3654 a promising treatment for myelofibrosis?The information provided does not directly mention TP-3654, so we can't determine if it's promising based on this data. However, other drugs like fedratinib and ruxolitinib have shown positive results in treating myelofibrosis, suggesting that new treatments like TP-3654 could also hold promise.36101415
What safety data is available for the treatment TP-3654 (Nuvisertib, SGI-9481) for Myelofibrosis?The provided research does not contain any safety data for TP-3654, Nuvisertib, or SGI-9481. The studies focus on antiemetic therapies for chemotherapy-induced nausea and vomiting, unrelated to TP-3654 or its other names.147911
What data supports the idea that Oral TP-3654 for Myelofibrosis is an effective treatment?The available research does not provide any data on the effectiveness of Oral TP-3654 for Myelofibrosis. Instead, the studies focus on a different drug, tofacitinib, which is used for treating rheumatoid arthritis and other conditions. Therefore, there is no information here to support the effectiveness of Oral TP-3654 for Myelofibrosis.2581213
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications. However, you cannot have received systemic antineoplastic therapy or experimental therapy within 2 weeks or 5 half-lives before starting the trial. For the Nuvisertib + Momelotinib Arm, if you are on a JAK inhibitor like ruxolitinib, it must be tapered over at least 1 week. Systemic steroids over 10 mg daily prednisone or equivalent must be stopped 1 week prior. Check with the trial team for specific medications.
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
My spleen is enlarged, confirmed by a doctor's exam or imaging tests.
My kidney function is within the required range.
I can take care of myself but might not be able to do heavy physical work.
I have at least 2 symptoms of my condition that can be measured.
My liver functions and blood clotting levels are within the required range.
My recent tests show significant scarring in my bone marrow.
I have been diagnosed with a type of myelofibrosis and it's considered intermediate or high-risk.
My white blood cell count is healthy without needing medication to help.
I can take care of myself but might not be able to do heavy physical work.
Exclusion Criteria
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.
I am eligible for a bone marrow or stem cell transplant within 3 months after joining.
I do not have brain cancer, cancer spread to the brain, or any condition affecting my nervous system.
I have taken hydroxyurea or anagrelide in the last 24 hours.
I have severe COPD with low oxygen levels.
My blood cancer involves more than 10% of certain blood cells.
I have not had major surgery within the last 2 weeks.
I have not had a heart attack or severe heart failure in the last 6 months.
I am on a blood thinner higher than 81mg aspirin or other types.
I have had portal hypertension or related complications.
I haven't had any cancer except for skin, prostate, or cervical cancer in the last 3 years.
I have a condition or had surgery that affects how my body absorbs food.
I have had a stem cell transplant before.
Treatment Details
The 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.
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:
Hoag Family Cancer InstituteNewport Beach, CA
Emory UniversityAtlanta, GA
University of ChicagoChicago, IL
Washington University of MedicineSaint Louis, MO
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
A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy. [2018]This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients.
Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. [2022]To compare the efficacy, safety, and tolerability of 5 doses of oral tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response to disease-modifying antirheumatic drugs.
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.
A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. [2023]Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways.
Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. [2022]To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).
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
Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy in the SENRI trial: analysis of risk factors for vomiting and nausea. [2018]We previously reported in the SENRI trial on the usefulness of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in colorectal cancer patients receiving an oxaliplatin-based regimen which is classified as moderately emetogenic cancer chemotherapy. In the present subgroup analysis of the SENRI trial, we assessed the risk factors for CINV in colorectal cancer patients who received oxaliplatin-based chemotherapy.
Efficacy and Safety of a Tofacitinib-based Immunosuppressive Regimen After Kidney Transplantation: Results From a Long-term Extension Trial. [2022]Tofacitinib is an oral Janus kinase inhibitor. This open-label, long-term extension (LTE) study (NCT00658359) evaluated long-term tofacitinib treatment in stable kidney transplant recipients (n = 178) posttransplant.
One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients. [2021]Label="PURPOSE" NlmCategory="OBJECTIVE">Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK1 receptor antagonist (NK1-RA), a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK1-RA, netupitant, and second-generation 5HT3-RA, palonosetron. So far, no data has been published in literature about the efficacy of a single dose of NEPA in MD-CT.
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.
Antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting: An updated systematic review and meta-analysis. [2022]To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice.
Efficacy, retention, and safety of tofacitinib in real-life: Hur-bio monocentric experience [2023]To assess the real-life efficacy, retention rate, and safety data of tofacitinib in rheumatoid arthritis (RA) patients.
Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies. [2021]Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. We evaluated radiographic progression in tofacitinib-treated patients with RA for up to 3 years in two pooled long-term extension (LTE) studies (ORAL Sequel; A3921041) (primary analysis), and for up to 5 years using data integrated from one phase (P)2 (A3921068), two P3 (ORAL Start; ORAL Scan) and two LTE studies (exploratory analysis).
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.
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.