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RecruitingLast updated: 15 February 2024

This study is assessing how safe and tolerable a new drug (called TP-3654) is in people with intermediate or high-risk primary or secondary myelofibrosisA 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

Clinical summary

Summary

This study will enrol people who have been previously treated and failed on a JAK inhibitor or who are ineligible to receive ruxolitinib or fedratinib.

Eligible participants will receive the experimental drug, called TP-3654, which is an oral PIM inhibitor.

Conditions

This trial is treating patients with myelofibrosis

Cancer

Blood Cancers Haematological

Age

People18+

Phase

I/II

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Sumitomo Pharma America, Inc.

Scientific 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

Eligibility

Inclusion

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.

Exclusion

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).

Inclusion

  • You are able to swallow medication by mouth.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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