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A Study of Oral TP-3654 in Patients With Myelofibrosis

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ClinicalTrials.gov Identifier: NCT04176198
Recruitment Status : Recruiting
First Posted : November 25, 2019
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

Tracking Information
First Submitted Date  ICMJE November 8, 2019
First Posted Date  ICMJE November 25, 2019
Last Update Posted Date June 15, 2021
Actual Study Start Date  ICMJE December 16, 2019
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2019)
  • Determine the incidence of dose-limiting toxicities (DLTs) at escalated doses of TP-3654 [ Time Frame: 28 days ]
  • Determine the incidence of treatment emergent adverse events [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2020)
  • Determine the incidence of QT interval changes and morphology as assessed by holter electrocardiogram (ECG) monitoring [ Time Frame: 25 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Half-life (t½) [ Time Frame: 24 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Peak Plasma Concentration (Cmax) [ Time Frame: 24 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Time of Maximum concentration observed (tmax) [ Time Frame: 24 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 hours ]
  • Assess patients for any evidence of Preliminary activity by proportion of patients with responses in complete remission, partial remission, clinical improvement, progressive disease and stable disease [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2019)
  • Determine the incidence of QT interval changes and morphology as assessed by intensive electrocardiogram (ECG) monitoring [ Time Frame: 25 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Half-life (t½) [ Time Frame: 24 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Peak Plasma Concentration (Cmax) [ Time Frame: 24 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Time of Maximum concentration observed (tmax) [ Time Frame: 24 hours ]
  • Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 hours ]
  • Assess patients for any evidence of Preliminary activity by proportion of patients with responses in complete remission, partial remission, clinical improvement, progressive disease and stable disease [ Time Frame: 12 months ]
Current Other Pre-specified Outcome Measures
 (submitted: November 22, 2019)
Study potential pharmacodynamic (PD) markers of TP-3654 [ Time Frame: 12 months ]
Evaluate exploratory biomarkers in peripheral blood samples and bone marrow biopsy samples
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study of Oral TP-3654 in Patients With Myelofibrosis
Official Title  ICMJE A Phase 1, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-3654 in Patients With Intermediate-2 and High-Risk Primary or Secondary Myelofibrosis
Brief Summary This study is a Phase 1, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of TP-3654 in patients with intermediate-2 and high-risk primary or secondary MF.
Detailed Description This study will enroll patients who have been previously treated and failed on a JAK inhibitor or ineligible to receive ruxolitinib or fedratinib.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Intermediate-2 Myelofibrosis
  • High-Risk Primary Myelofibrosis
  • High-Risk Secondary Myelofibrosis
Intervention  ICMJE Drug: TP-3654
Oral PIM Inhibitor
Study Arms  ICMJE Experimental: TP-3654
Intervention: Drug: TP-3654
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 14, 2021)
60
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2019)
50
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Patients must meet all of the following inclusion criteria to be eligible:

  • Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF as per WHO diagnostic criteria and intermediate-2 or high-risk primary or secondary MF based on the Dynamic International Prognostic Scoring System (DIPSS)
  • Previously treated with a JAKi and failed on a JAK inhibitor or are ineligible to be treated with Ruxolitinib or Fedratinib at the discretion of the investigator
  • Grade ≥ 2 bone marrow fibrosis, as confirmed by bone marrow biopsy within 12 weeks prior to Screening

Fulfill the following laboratory parameters:

  • Platelet count ≥ 50 X 10^9 /L, without the assistance of growth factors or platelet transfusions
  • Absolute Neutrophil Count (ANC) ≥ 1 x 10^9/L without the assistance of granulocyte growth factors
  • Peripheral blood blast count < 10%
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Life expectancy ≥ 3 months
  • Adequate renal function, as determined by clinical laboratory tests (serum creatinine ≤ 1.5 x upper limit of normal (ULN), and calculated creatinine clearance ≥ 30 mL/min) (Cockcroft-Gault)
  • Adequate hepatic function (ALT/AST ≤ 3 x ULN, total bilirubin ≤ 1.5 x ULN; or ALT/AST ≤ 5 x ULN, direct bilirubin ≤ 2 x ULN if due to myelofibrosis), and coagulation ([PT and PTT] ≤ 1.5 x ULN)
  • Agree to provide bone marrow biopsies during the study: at baseline or within 12 weeks prior to enrollment, and every 6 months during treatment.
  • Splenomegaly during the screening period as demonstrated by splenic length ≥ 5 cm below the costal margin by palpation or spleen volume of ≥ 450 cm3 by Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scan
  • Show at least 2 symptoms measurable (score ≥ 1) using the MFSAF, v4.0.

Patients meeting any one of these exclusion criteria will be prohibited from participating in this study:

  • Received previous systemic antineoplastic therapy (including unconjugated therapeutic antibodies, toxin immunoconjugates, ESA, and alpha-interferon) or any experimental therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
  • Major surgery within 2 weeks before the first dose of either study drug.
  • Splenic irradiation within 6 months prior to Screening or prior splenectomy.
  • AML, MDS, or peripheral blasts ≥ 10%.
  • Prior autologous or allogeneic stem cell transplant at any time.
  • Eligible for allogeneic bone marrow or stem cell transplantation within 3 months following enrollment.
  • Experiencing electrolyte abnormalities of NCI CTCAE Grade ≥ 2 unless they can be corrected during screening and are deemed not clinically significant by the Investigator.
  • History of congestive heart failure, myocardial infarction within the past 6 months prior to Cycle 1/Day 1; left ventricular ejection fraction < 45% by echocardiogram or MUGA, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1/Day 1.
  • Corrected QT interval (using Fridericia's correction formula) of > 450 msec in men and > 470 msec in women.
  • Central nervous system (CNS) cancer or metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (eg, unstable vertebral metastases).
  • Other invasive malignancies within the last 3 years, except non-melanoma skin cancer, and localized cured prostate and cervical cancer
  • Experienced portal hypertension or any of its complications.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic antimicrobial within 14 days.
  • Known bleeding diathesis or signs of uncontrolled active bleeding (hematuria, GI bleeding) other than self-limited causes of benign etiology that have been adequately investigated at the discretion of the Investigator.
  • Requiring anticoagulation with aspirin > 81mg daily, unfractionated heparin, low molecular weight heparin (LMWH), direct anti-thrombin inhibitors, or vitamin K antagonists (eg, warfarin).
  • Severe chronic obstructive pulmonary disease with hypoxemia (defined as resting O2 saturation of < 90% breathing room air).
  • Medical condition or have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption.
  • Used hydroxyurea or anagrelide within 24 hours prior to the first dose.
  • Systemic steroid therapy (>10 mg daily prednisone or equivalent) within 7 days prior to the first dose of study treatment (note: topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tegan Nguyen 617-674-8745 tnguyen@bostonbiomedical.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04176198
Other Study ID Numbers  ICMJE BBI-TP-3654-102
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sumitomo Dainippon Pharma Oncology, Inc
Study Sponsor  ICMJE Sumitomo Dainippon Pharma Oncology, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sumitomo Dainippon Pharma Oncology, Inc
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP