Clinical Trials /

A Study of Oral TP-3654 in Patients With Myelofibrosis

NCT04176198

Description:

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.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
  • Secondary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Oral TP-3654 in Patients With Myelofibrosis
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BBI-TP-3654-102
  • NCT ID: NCT04176198

Conditions

  • Intermediate-2 Myelofibrosis
  • High-Risk Primary Myelofibrosis
  • High-Risk Secondary Myelofibrosis

Interventions

DrugSynonymsArms
TP-3654TP-3654

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
TP-3654Experimental
  • TP-3654

Eligibility Criteria

        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 MF23, as confirmed by bone marrow biopsy within 12 weeks prior to Screening

        Fulfill the following laboratory parameters:

          -  Platelet count > 50 X 109 /L, without the assistance of growth factors or platelet
             transfusions

          -  Absolute Neutrophil Count (ANC) ≥ 1 x 109/L without the assistance of granulocyte
             growth factors

          -  Hemoglobin ≥ 8 g/dL

          -  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 ≥60 mL/min)
             (Cockcroft-Gault)

          -  Adequate hepatic function (ALT/AST < 2.5 x ULN, bilirubin < 1.5 x ULN), and
             coagulation ([PT and PTT] < 1.5 x ULN)

          -  Agree to provide 3 bone marrow biopsies during the study: at baseline or within 12
             weeks prior to enrollment, and every 6 months post-treatment.

          -  Splenomegaly during the screening period as demonstrated by splenic length ≥ 5 cm 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, and alpha-interferon) or any experimental therapy
             within 14 days or 5 half-lives, whichever is shorter, 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. 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
             therapy.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the incidence of dose-limiting toxicities (DLTs) at escalated doses of TP-3654
Time Frame:28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Determine the incidence of QT interval changes and morphology as assessed by intensive electrocardiogram (ECG) monitoring
Time Frame:25 hours
Safety Issue:
Description:
Measure:Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Half-life (t½)
Time Frame:24 hours
Safety Issue:
Description:
Measure:Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Peak Plasma Concentration (Cmax)
Time Frame:24 hours
Safety Issue:
Description:
Measure:Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Time of Maximum concentration observed (tmax)
Time Frame:24 hours
Safety Issue:
Description:
Measure:Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Area under the plasma concentration versus time curve (AUC)
Time Frame:24 hours
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sumitomo Dainippon Pharma Oncology, Inc

Last Updated

July 20, 2020