A Study of Oral TP-3654 in Patients With Myelofibrosis

• Status: Recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

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 or high-risk primary or secondary MF.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Boston Biomedical, Inc; Sumitomo Dainippon Pharma Oncology, Inc

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 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).