A Phase I/II, Open-Label Study Evaluating Twice-Daily Administration of CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis
- Diagnosis of PMF or post-ETIPV MF as per revised World Health Organization (WHO)
criteria (Section 16.4, Appendix 3).
- High-risk or Intermediate-2 risk MF (as defined by the International Prognostic
Scoring System [IPSS]; Section 16.6, Appendix 5); or Intermediate-1 risk MF (IPSS)
associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to
- 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
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
2 (Section 16.3, Appendix 2).
- Must have evidence of acceptable organ function within 7 days of initiating study
drug as evidenced by the following:
- SGOT (AST) or SGPT (ALT) less than or equal 2.5 x upper limit of normal(ULN) (or less
than or equal to 5 x ULN if in the investigator's opinion the elevation is due to
- Direct Bilirubin less than or equal to 2.0 x ULN
- Serum creatinine less than or equal to 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.
- Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g.,
thalidomide), immunosuppressive therapy, corticosteroids >10 mg/day prednisone or
equivalent, or growth factor treatment (e.g., 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
(i.e., 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.
- Positive serologic testing for hepatitis B (HBsAg and HBcAb total) and hepatitis 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 participate at the Investigator's
- Any acute active infection.
- Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia)
interval to >480 at pre-study screening, unless attributable to pre-existing bundle
- 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 intercurrent illness or any concurrent condition that, in the
Investigator's opinion, would jeopardize the safety of the patient or compliance with