Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)

Not Recruiting

Trial ID: NCT00935987

Purpose

This study seeks to (i) determine a safe and tolerated dose of CYT387 (momelotinib) given to patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.

Official Title

A Phase I/II, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally-Administered CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis.

Stanford Investigator(s)

Jason Gotlib

Professor of Medicine (Hematology)

Eligibility

Inclusion Criteria:

* Diagnosis of PMF or post-polycythemia Vera (PV) or post-essential Thrombocythemia (ET) MF as per revised World Health Organization (WHO) criteria.
* High-risk or Intermediate-2 risk MF (as defined by the International Prognostic Scoring System \[IPSS\]; Appendix 13.6); or intermediate-I risk MF (IPSS) associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy.
* Must be at least 18 years of age with life expectancy of ≥ 12 weeks.
* Must be able to provide informed consent and be willing to sign an informed consent form.
* Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
* Must have evidence of acceptable organ function within 7 days of initiating study drug as evidenced by the following:

* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis)
* Bilirubin ≤ 2.0 x ULN or direct bilirubin \< 1.0
* Serum creatinine ≤ 2.5 x ULN
* Absolute neutrophil count ≥ 500/µL
* Platelet count ≥ 50,000/µL
* Females of childbearing potential must have a negative pregnancy test within 4 days of initiating study drug.

Exclusion Criteria:

* Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide), immunosuppressive therapy, corticosteroids \> 10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin) within 14 days prior to initiation of study drug.
* Incomplete recovery from major surgery within four weeks of study entry.
* Radiation therapy within four weeks of study entry.
* Women of childbearing potential, unless surgically sterile for at least 3 months (ie, hysterectomy), OR postmenopausal for at least 12 months (FSH \> 30 U/mL), OR unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
* Men who partner with a woman of childbearing potential, unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through to the end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
* Females who are pregnant or are currently breastfeeding.
* Known positive status for HIV.
* Clinically active hepatitis B or C.
* Diagnosis of another malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ or superficial bladder cancer may be eligible to participate at the Investigator's discretion.
* Any acute active infection.
* Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia) interval to \> 450 msec for males or \> 470 msec for females at prestudy screening, unless attributable to pre-existing bundle branch block.
* Presence of ≥ Grade 2 peripheral neuropathy.
* Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism within 3 months prior to initiation of study drug.
* Uncontrolled inter current illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.

Intervention(s):

drug: CYT387

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office
650-498-7061

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