PRIMARY OBJECTIVES:
I. To evaluate overall response rate.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis (MF) (per common terminology criteria for adverse events, version 4.03).
II. To evaluate the efficacy of imetelstat in the reduction of spleen size, as measured by physical examination (palpable distance from the left costal margin).
III. To evaluate the efficacy of imetelstat in inducing red blood cell transfusion-independence in previously transfusion-dependent patients (per International Working Group for Myelofibrosis Research and Treatment [IWG-MRT] criteria).
TERTIARY OBJECTIVES:
I. To evaluate the effect of imetelstat on bone marrow histology and karyotype. II. To evaluate the effect of imetelstat on leukocytosis and thrombocytosis.
OUTLINE: Patients receive imetelstat sodium intravenously (IV) over 2 hours on day 1. Treatment repeats every 21 days for up to 52 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Inclusion Criteria:
- Diagnosis of one of the following:
- PMF per the revised World Health Organization (WHO) criteria
- Post-ET/PV MF per the IWG-MRT criteria
- High-risk or Intermediate-2 risk MF (as defined by the Dynamic International Prognostic Scoring System [DIPSS-plus])
- Life expectancy of >= 12 weeks
- Able to provide informed consent and be willing to sign an informed consent form
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 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)
- Serum glutamic pyruvate transaminase (SGPT) 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)
- Total bilirubin =< 3.0 mg/dL (or direct bilirubin < 1 mg/dL)
- Creatinine =< 3.0 mg/dL
- Absolute neutrophil count >= 1000/uL
- Platelet count >= 50,000/uL
- Absence of active treatment with systemic anticoagulation and a baseline prothrombin time (PT) and activated partial thromboplastin time (aPTT) that does not exceed 1.5 x ULN
- Females of childbearing potential must have a negative pregnancy test =< 7 days prior to registration, unless they are surgically sterile for at least 3 months (i.e., hysterectomy), OR postmenopausal for at least 12 months (follicle-stimulating hormone [FSH] >30 U/mL)
- Females of childbearing potential must 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
- Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through follow-up; permitted methods for preventing pregnancy should be communicated to the subjects and their understanding confirmed
Exclusion Criteria:
- Females who are pregnant or are currently breastfeeding
- Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent, growth factor treatment (e.g., erythropoietin) or Janus kinase (JAK) inhibitor therapy =< 14 days prior to registration
- Subjects with another active malignancy
- Note: patients with early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin or cervical intraepithelial neoplasia are eligible for enrollment
- Known positive status for human immunodeficiency virus (HIV)
- Any unresolved toxicity greater or equal to grade 2 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve
- Incomplete recovery from any prior surgical procedures or had surgery =< 4 weeks prior to registration, excluding the placement of vascular access
- Presence of acute active infection requiring antibiotics
- Uncontrolled intercurrent illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
Last updated: 11/18/2012
NCT ID: NCT01731951
IRB Number:12-005104
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