Imetelstat Sodium in Treating Patients With Primary or Secondary Myelofibrosis
This pilot clinical trial studies how well imetelstat sodium works in treating patients with primary or secondary myelofibrosis and other myeloid malignancies. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth
Drug: imetelstat sodium
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Myelofibrosis and Other Myeloid Malignancies|
- MF patients: Overall response rate defined as a clinical improvement (CI), partial remission (PR), or complete remission (CR) according to the IWG-MRT consensus criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]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.
- MDS patients: Overall response rate according to the IWG response criteria in myelodysplasia [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]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.
- Maximum grade for each type of adverse event for each patient [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
- Spleen response defined as either a minimum 50% reduction in palpable splenomegaly of a spleen that is at least 10 cm at baseline or a spleen that is palpable at more than 5 cm at baseline becomes not palpable [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Will be calculated by the number of patients who achieve spleen response divided by the total number of evaluable patients with spleen involvement at baseline (estimated to be approximately 80% of patients). Ninety-five percent exact binomial confidence intervals for the true proportion of patients with spleen response will be calculated.
- Proportion of patients achieving transfusion independence [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Will be estimated by the number of patients who achieve transfusion independence divided by the total number of evaluable patients who were transfusion dependent at baseline Ninety-five percent exact binomial confidence intervals for the true proportion of patients who become transfusion independent will be calculated.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose & schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication.
Drug: imetelstat sodium
I. To evaluate overall response rate.
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 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
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 be treated for up to 3 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01731951
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Ayalew Tefferi, M.D.||Mayo Clinic|