Imetelstat Sodium in Treating Patients With Primary or Secondary Myelofibrosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01731951
First received: November 18, 2012
Last updated: June 18, 2015
Last verified: June 2015
  Purpose

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


Condition Intervention Phase
Primary Myelofibrosis
Secondary Myelofibrosis
Myeloid Malignancies
Drug: Imetelstat
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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.

  • 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.


Secondary Outcome Measures:
  • 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).

  • 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.


Enrollment: 56
Study Start Date: November 2012
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Myelofibrosis (MF) participants will receive Imetelstat, 9.4 milligram per kilogram (mg/kg), intravenously [IV] as 2 hour infusion, on Day 1 of every 21-day cycle up to 3 years until disease progression or unacceptable toxicity.
Drug: Imetelstat
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.
Other Name: GRN163L
Experimental: Arm B
MF participants will receive Imetelstat, 9.4mg/kg, IV as 2 hour infusion, on Day 1, 8, 15 of Cycle 1, then Day 1 of each subsequent 21-day cycle up to 3 years until disease progression or unacceptable toxicity.
Drug: Imetelstat
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.
Other Name: GRN163L
Experimental: Arm D
Blast phase MF participants will receive Imetelstat, 9.4mg/kg, IV as 2 hour infusion, on Day 1, 8, 15, 22 of every 28-day cycle up to 3 years until disease progression or unacceptable toxicity.
Drug: Imetelstat
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.
Other Name: GRN163L
Experimental: Arm E
MF participants with spliceosome mutations or ring sideroblasts will receive Imetelstat, 7.5mg/kg, IV as 2 hour infusion, on Day 1 of every 28-day cycle.
Drug: Imetelstat
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.
Other Name: GRN163L
Experimental: Arm F
MF participants with spliceosome mutations or ring sideroblasts will receive Imetelstat, 9.4mg/kg on Day1 of every 28-day cycle.
Drug: Imetelstat
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.
Other Name: GRN163L
Experimental: Arm G
Myelodysplastic syndromes (MDS)/ myeloproliferative neoplasm (MPN) or MDS participants with spliceosome mutations or ring sideroblasts will receive Imetelstat, 7.5mg/kg on Day 1 of every 28-day cycle.
Drug: Imetelstat
Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.
Other Name: GRN163L

Detailed Description:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01731951

Locations
United States, Minnesota
Rochester, Minnesota, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01731951     History of Changes
Other Study ID Numbers: CR107110, CP14B019
Study First Received: November 18, 2012
Last Updated: June 18, 2015
Health Authority: United States: Food and Drug Administration
United States: Ministry of Food and Drug Safety
United States: Centralna Ewidencja Badań Klinicznych
United States: U.S. Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Myelofibrosis
Myelodysplastic Syndromes
Myeloproliferative Neoplasm
Imetelstat
GRN163L

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Primary Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on July 28, 2015