Imetelstat Sodium in Treating Patients With Primary or Secondary Myelofibrosis

PRIMARY OBJECTIVES:

I. To evaluate overall response rate.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis
(MF).

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 improving anemia or inducing red blood cell
transfusion-independence in previously transfusion-dependent patients (per International
Working Group for Myelofibrosis Research and Treatment [IWG-MRT] criteria).

IV. To evaluate onset and durability of response as defined in primary and secondary
endpoints

EXPLORATORY OBJECTIVES:

I. To evaluate the effect of imetelstat on bone marrow histology, karyotype and JAK2V617F
allele burden II. To evaluate the effect of imetelstat on leukocytosis, circulating blast
count, circulating immature myeloid cell count and thrombocytosis.

OUTLINE: Patients receive imetelstat sodium intravenously (IV) over 2 hours on day 1.
Patients may continue to receive imetelstat study treatment for as long as they derive
clinical benefit or until study end. The study will end when all patients have discontinued
study drug, the last patient enrolled has been treated for 5 years, or imetelstat is
commercially available in the United States, whichever occurs first.

After completion of study treatment, patients are followed up every 6 months for 5 years.

Inclusion Criteria:

- Diagnosis of one of the following:

- primary myelofibrosis (PMF) per the revised World Health Organization (WHO)
criteria

- post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-ET/PV MF)
per the International Working Group for Myeloproliferative Neoplasms Research and
Treatment (IWG-MRT) criteria

- High-risk or Intermediate-2 risk MF (as defined by the Dynamic International
Prognostic Scoring System [DIPSS-plus])

- Life expectancy of greater than or equal to (>=) 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/microliter (mcL)

- Platelet count >= 50,000/mcL

- 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