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A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Patients With DIPSS_plus Intermediate-2 or High Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF).


N/A
18 Years
N/A
Open (Enrolling)
Both
Primary Myelofibrosis, Secondary Myelofibrosis

Thank you

Trial Information

A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Patients With DIPSS_plus Intermediate-2 or High Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF).


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate defined as a clinical improvement (CI), partial remission (PR), or complete remission (CR) according to the IWG-MRT consensus criteria

Outcome Description:

Will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent Duffy Santner confidence intervals for the true success proportion will be calculated.

Outcome Time Frame:

Up to 27 weeks

Safety Issue:

No

Principal Investigator

Ayalew Tefferi, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

MC1285

NCT ID:

NCT01731951

Start Date:

October 2012

Completion Date:

Related Keywords:

  • Primary Myelofibrosis
  • Secondary Myelofibrosis
  • Primary Myelofibrosis
  • Thrombocythemia, Essential

Name

Location

Mayo ClinicRochester, Minnesota  55905