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Trial record 1 of 1 for:    "NCT04176198"
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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 : March 2, 2023
Information provided by (Responsible Party):
Sumitomo Pharma Oncology, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: TP-3654 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 16, 2019
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : July 2024

Arm Intervention/treatment
Experimental: TP-3654 Drug: TP-3654
Oral PIM Inhibitor

Primary Outcome Measures :
  1. 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

  2. Determine the incidence of treatment emergent adverse events [ Time Frame: 28 days ]
    Frequency, severity, and causal relationship of adverse events

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Determine the change in Patient Global Impression of Change (PGIC) at week 24 [ Time Frame: 24 weeks ]
    Change in PGIC score during treatment

  6. Assess the reduction in bone marrow fibrosis in repeat biopsies [ Time Frame: 12 months ]
    Change in bone marrow fibrosis during treatment compared to baseline

  7. Determine Overall Survival [ Time Frame: 3 years ]
    The time interval from treatment start date of death from any cause

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

Other Outcome Measures:
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04176198

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Contact: Nanci McClellan 236-818-5990 nanci.mcclellan@oncology.sumitomo-pharma.com
Contact: Paula Minnick paula.minnick@oncology.sumitomo-pharma.com

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United States, Arizona
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Audrey Johnson    520-694-9084    audieejayy@arizona.edu   
United States, Florida
University of Florida Health Shands Cancer Hospital Completed
Gainesville, Florida, United States, 32608
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Alessia Zoso    305-243-0327    azoso@miami.edu   
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Jason Brecher    551-966-5274    jason.brecher@hmhn.org   
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: Katherine Collins       katherine.collins@roswellpark.org   
United States, North Carolina
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Ben Dosan       benjamin.dosan@duke.edu   
United States, Virginia
University of Virginia Cancer Center Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Kelly Reed    434-297-7783    yvy8ge@hscmail.mcc.virginia.edu   
Aichi Medical University Hospital Recruiting
Aichi, Japan
Contact: Akiyoshi Takami    0561-62-3311    takami.akiyoshi.490@mail.aichi-med-u.ac.jp   
National Cancer Center Hospital East Recruiting
Chiba, Japan
Contact: Junichiro Yuda, MD    04-7133-1111    jyuda@east.ncc.go.jp   
University of Miyazaki Hospital Recruiting
Miyazaki, Japan
Contact: Kazuya Shimoda, MD    0985-85-1510    kshimoda@med.miyazaki-u.ac.jp   
Osaka University Hospital Recruiting
Osaka, Japan
Contact: Michiko Ichii, MD    06-6879-5111    michii@bldon.med.osaka-u.ac.jp   
Saitama Medical Center Recruiting
Saitama, Japan
Contact: Takayuki Tabayashi    049-228-3411    ttabaya@saitama-med.ac.jp   
Shizuoka Cancer Center Recruiting
Shizuoka, Japan
Contact: Masafumi Fukaya, MD    055-989-5222    m.fukaya@scchr.jp   
Juntendo University Hospital Recruiting
Tokyo, Japan
Contact: Shuichi Shirane, MD    03-3813-3111    sshirane@juntendo.ac.jp   
Sponsors and Collaborators
Sumitomo Pharma Oncology, Inc.
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Responsible Party: Sumitomo Pharma Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04176198    
Other Study ID Numbers: BBI-TP-3654-102
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: March 2, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases