A Study of Oral TP-3654 in Patients With Myelofibrosis

November 20, 2023 updated by: Sumitomo Pharma America, Inc.

A Phase 1/2, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-3654 in Patients With Intermediate or High-Risk Primary or Secondary Myelofibrosis

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Adelaide, Australia
        • Not yet recruiting
        • Icon Cancer Centre (Ashford Cancer Centre Research)
        • Contact:
    • South Australia
      • Adelaide, South Australia, Australia
    • Victoria
      • Box Hill, Victoria, Australia
  • Japan
      • Aichi, Japan
      • Chiba, Japan
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
      • Miyazaki, Japan
      • Osaka, Japan
      • Saitama, Japan
      • Shizuoka, Japan
        • Recruiting
        • Shizuoka Cancer Center
        • Contact:
      • Tokyo, Japan
        • Recruiting
        • Juntendo University Hospital
        • Contact:
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University Of Alabama
        • Contact:
          • Tiffany Hill
          • Phone Number: 205-934-9591
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • The University of Arizona Cancer Center
        • Contact:
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
    • Florida
      • Gainesville, Florida, United States, 32608
        • Completed
        • University of Florida Health Shands Cancer Hospital
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center at Hackensack University Medical Center
        • Contact:
    • New York
      • Buffalo, New York, United States, 14263
      • New York, New York, United States, 10029
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Weill Cornell Medical Center
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
    • Tennessee
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Houston, Texas, United States, 77054
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Not yet recruiting
        • Huntsman Cancer Institute
        • Contact:
          • Emerson Lebleu
          • Phone Number: 801-587-9703
    • Virginia
      • Charlottesville, Virginia, United States, 22903

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 or high-risk primary or secondary MF based on the Dynamic International Prognostic Scoring System (DIPSS)
  • Previously treated with a JAK inhibitor 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 ≥ 25 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 MF-SAF, 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TP-3654
Drug: TP-3654
Oral PIM Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the incidence of dose-limiting toxicities (DLTs) at escalated doses of TP-3654
Time Frame: 28 days
Frequency, severity, and causal relationship of study defined high grade toxicities
28 days
Determine the incidence of treatment emergent adverse events
Time Frame: 28 days
Frequency, severity, and causal relationship of adverse events
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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: 24 weeks
Number of patients achieving objective response by IWG-MRT response criteria
24 weeks
Determine proportion of patients who have ≥ 25% spleen volume reduction at week 24
Time Frame: 24 weeks
Number of patients who have ≥ 25% spleen volume reduction compared to baseline after 24 weeks of treatment
24 weeks
Determine proportion of patients who have ≥ 35% spleen volume reduction (SVR35) at week 24
Time Frame: 24 weeks
Number of patients who have ≥ 35% spleen volume reduction compared to baseline after 24 weeks of treatment
24 weeks
Determine proportion of patients with ≥ 50% improvement in total symptom score (TSS50) at week 24
Time Frame: 24 weeks
Number of patients who have ≥ 50% total symptom score reduction by MFSAF compared to baseline after 24 weeks of treatment
24 weeks
Determine the change in Patient Global Impression of Change (PGIC) at week 24
Time Frame: 24 weeks
Change in PGIC score during treatment
24 weeks
Assess the reduction in bone marrow fibrosis in repeat biopsies
Time Frame: 12 months
Change in bone marrow fibrosis during treatment compared to baseline
12 months
Determine Overall Survival
Time Frame: 3 years
The time interval from treatment start date of death from any cause
3 years
Determine the incidence of QT interval changes and morphology as assessed by holter electrocardiogram (ECG) monitoring
Time Frame: 25 hours
Changes in QT interval and heart rhythm
25 hours
Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Half-life (t½)
Time Frame: 24 hours
The estimate of time for the TP-3654 concentration or amount to be reduced by half
24 hours
Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Peak Plasma Concentration (Cmax)
Time Frame: 24 hours
The maximum TP-3654 concentration after administration
24 hours
Establish the pharmacokinetic (PK) parameters of TP-3654 by assessing Time of Maximum concentration observed (tmax)
Time Frame: 24 hours
The estimate of time to maximum TP-3654 concentration
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
The amount of drug exposure over 24 hours period after administration
24 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study potential pharmacodynamic (PD) markers of TP-3654
Time Frame: 12 months
Evaluate exploratory biomarkers in peripheral blood samples and bone marrow biopsy samples. Change in protein phosphorylation and inflammatory cytokines.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sumitomo Pharma America, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 16, 2019

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

November 8, 2019

First Submitted That Met QC Criteria

November 22, 2019

First Posted (Actual)

November 25, 2019

Study Record Updates

Last Update Posted (Actual)

November 21, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBI-TP-3654-102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelofibrosis

Clinical Trials on TP-3654

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Saudi Arabia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe