A Phase 2 Study With IPI-926 in Patients With Myelofibrosis

A Phase 2 Study of IPI-926 in Patients With Myelofibrosis

The purpose of this study is to determine the safety and efficacy of IPI-926 in patients with myelofibrosis (MF) (primary myelofibrosis [PMF], post-polycythemia vera myelofibrosis [post-PV MF], or post-essential thrombocythemia myelofibrosis [post-ET MF]).

Study Overview

• Status: Completed
• Conditions: Primary Myelofibrosis; Fibrosis, Bone Marrow
• Intervention / Treatment: Drug: IPI-926

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Arizona Mayo Clinic
  • California
    • Palo Alto, California, United States, 94025
      • Stanford University School of Medicine, Division of Hematology
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥18 years of age at the time of signing the ICF.
• Voluntarily sign an ICF.
• Pathologically confirmed PMF or post ET/PV MF as per the WHO diagnostic criteria (note that it must include at least Grade 1 marrow fibrosis, see Appendix 3) with intermediate-1, intermediate -2, or high risk disease according to the IWG prognostic scoring system (see Appendix 4). If patients have low risk disease, then they must have symptomatic splenomegaly that is ≥ 10 cm below left costal margin by physical exam.
• ECOG performance of 0-2.
• Life expectancy of at least 3 months.
• Recovery to Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia.
• If a woman, be of non-child bearing potential or, for women of child-bearing potential (WCBP) (defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months for women ≤55 years; for women >55 years 12 consecutive months), must have a negative serum or urine pregnancy test result within 2 weeks of first dose of study drug.
• All WCBP and all sexually active male patients must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception include use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, and total abstinence.
• Ability to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

• Prior treatment with any inhibitor of the hedgehog pathway (e.g. GDC-0449).
• Received any treatment for myelofibrosis within 2 weeks of study entry.
• Other invasive malignancies diagnosed within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer.
• Inadequate hepatic function defined by:
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN).
• Direct bilirubin >1.5 x ULN.
• Cirrhotic liver disease, ongoing alcohol abuse, or known chronic active or acute hepatitis.
• Inadequate renal function defined by serum creatinine >2 x ULN.
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
• Presence of active infection or systemic use of antibiotics within 72 hours of treatment.
• Significant co-morbid condition or disease, which in the judgment of the Investigator, would place the patient at undue risk or interfere with the study.
• Known human immunodeficiency virus (HIV) positivity.
• Known hypersensitivity to IPI-926, or any of the excipients in IPI-926 capsules.
• Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IPI-926; Single Arm, Phase 2 trial evaluating the safety and efficacy of IPI-926 in patients with myelofibrosis	Drug: IPI-926; Single Arm study of oral IPI-926 at 160 mg, 130 mg or 110 mg daily, until progressive disease or intolerability to study treatments or withdrawal of ICF; Other Names: Hedgehog Inhibitor; Hedgehog Pathway Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the overall response rate of IPI-926, defined as clinical improvement (CI); partial remission (PR); and complete remission (CR), according to the International working group (IWG) criteria in patients with Myelofibrosis	At least 2 months

Collaborators and Investigators

• Sponsor: Infinity Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Srdan Verstovsek, M.D.; Ph.D, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 13, 2011

Study Record Updates

• Last Update Posted (Estimate): November 15, 2012
• Last Update Submitted That Met QC Criteria: November 14, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Myelofibrosis; IPI-926; 926; Hedgehog; Infinity Pharmaceuticals; Post Essential thrombocythemia; Post Polycythemia vera
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: IPI-926-08