Trial record 18 of 337 for:    "primary myelofibrosis"

Safety Study Evaluating Twice-Daily Administration of CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01423058
First received: July 7, 2011
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

The myeloproliferative neoplasms (MPN), most notably polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are a diverse but inter-related suite of clonal disorders of pluripotent hematopoietic stem cells (Tefferi et al., 2008). The MPN share a range of biological, pathological, and clinical features including the relative overproduction of one or more cells of myeloid origin, growth factor independent colony formation in vitro, marrow hypercellularity, extramedullary hematopoiesis, spleno- and hepatomegaly, and thrombotic and/or hemorrhagic diatheses (Tefferi et al., 2005).

This is a multi-centre, open-label, non-randomized, dose-escalation study, to be conducted in two phases: a dose-escalation phase (Part 1), to determine the safety and tolerability of CYT387, and to identify a therapeutic dose for the expanded cohort; and a dose-confirmation phase (Part 2), which will be a cohort expansion at or below the MTD of CYT387.

In the Part I dose-escalation phase of the study, subjects will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 200 mg BID (twice daily with doses taken approximately 12 hours apart). Doses will be escalated by 50 mg BID per cohort until dose-limiting toxicities are observed. The dose level at which ≥2 of 6 subjects develop a first cycle DLT is defined as the DLT level. The MTD is defined as the dose level below the DLT level. New dose levels may begin accrual only if all subjects at the current dose level have been observed for a minimum of 28 days from the first day of treatment. The dose level chosen for study in the dose confirmation phase of the study will be the MTD or a lower dose shown to have significant clinical activity (efficacy) as determined by the safety review committee. Subjects will be evaluated weekly for the first cycle, every 2 weeks during cycle 2, then monthly for 4 cycles for a total of 6 cycles.

In the dose-confirmation phase of the study, approximately fifty (50) subjects will be treated at the MTD or at a lower dose shown to have significant clinical activity (efficacy) as chosen by the Safety Review Committee. In the dose confirmation phase of the study subjects will be evaluated every 2 weeks during the first treatment cycle, and then monthly for 5 cycles for a total of 6 cycles.


Condition Intervention Phase
Primary Myelofibrosis
Post-Polycythemia Vera
Post-Essential Thrombocythemia Myelofibrosis
Drug: CYT387
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label Study Evaluating Twice-Daily Administration of CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • To determine the safety of CYT387 by characterization and relationship of adverse events, affects on vital signs and laboratory parameters, and QTc intervals as measured by electrocardiogram (ECG) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To determine maximum tolerated dose of CYT387 by characterization of Dose Limiting Toxicities [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To confirm the half-life of CYT387 by pharmacokinetic analyses [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To determine the efficacy of CYT387 by evaluation of spleen and liver size, disease related constitutional symptoms, transfusion dependence and anemia response. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the effect of CYT387 on JAK2V617F mutant allele burden via Polymerase Chain Reaction (PCR) analyses [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To determine the effect of CYT387 on plasma levels of inflammatory, fibrogenic and angiogenic cytokines via Enzyme-Linked Immunosorbant Assay (ELISA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To determine the effect of CYT387 on bone marrow or peripheral blood cytogenetic findings [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: August 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CYT387
CYT387
Drug: CYT387

In the Part I dose-escalation phase of the study, subjects will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 200 mg BID (twice daily with doses taken approximately 12 hours apart. Doses will be escalated by 50 mg BID in successive cohorts of 3 subjects per dose level. Subjects will be evaluated weekly for the first cycle, every 2 weeks during cycle 2, then monthly for 4 cycles for a total of 6 cycles.

In the dose confirmation phase of the study (Part 2), subjects will be evaluated every 2 weeks during the first treatment cycle, and then monthly for 5 cycles for a total of 6 cycles.


  Eligibility

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

Inclusion Criteria:

  • Diagnosis of PMF or post-ETIPV MF as per revised World Health Organization (WHO) criteria (Section 16.4, Appendix 3).
  • High-risk or Intermediate-2 risk MF (as defined by the International Prognostic Scoring System [IPSS]; Section 16.6, Appendix 5); or Intermediate-1 risk MF (IPSS) associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy.
  • Must be at least 18 years of age with life expectancy of ≥ 12 weeks.
  • Must be able to provide informed consent and be willing to sign an informed consent form.
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Section 16.3, Appendix 2).
  • Must have evidence of acceptable organ function within 7 days of initiating study drug as evidenced by the following:
  • SGOT (AST) or SGPT (ALT) less than or equal 2.5 x upper limit of normal(ULN) (or less than or equal to 5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis)
  • Direct Bilirubin less than or equal to 2.0 x ULN
  • Serum creatinine less than or equal to 2.5 x ULN
  • Absolute neutrophil count ≥ 500/µL
  • Platelet count ≥ 50,000/µL
  • Females of childbearing potential must have a negative pregnancy test within 4 days of initiating study drug.

Exclusion Criteria:

  • Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
  • Incomplete recovery from major surgery within four weeks of study entry.
  • Radiation therapy within four weeks of study entry.
  • Women of childbearing potential, unless surgically sterile for at least 3 months (i.e., hysterectomy), OR postmenopausal for at least 12 months (FSH > 30 U/mL), OR unless they 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.
  • Men who partner with a woman of childbearing potential, unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through to the end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
  • Females who are pregnant or are currently breastfeeding.
  • Known positive status for HIV.
  • Positive serologic testing for hepatitis B (HBsAg and HBcAb total) and hepatitis C (anti-HCV)
  • Diagnosis of another malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ or superficial bladder cancer may be eligible participate at the Investigator's discretion.
  • Any acute active infection.
  • Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia) interval to >480 at pre-study screening, unless attributable to pre-existing bundle branch block.
  • Presence of ≥ grade 2 peripheral neuropathy.
  • Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism within 3 months prior to initiation of study drug.
  • 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: NCT01423058

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Texas
MD Anderson Cancer Center, The University of Texas
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute at the University of Utah
Salt Lake City, Utah, United States, 84108
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Mark Kowalski, M.D. YM Biosciences Inc.
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01423058     History of Changes
Other Study ID Numbers: YM387-II-02
Study First Received: July 7, 2011
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocythemia, Essential
Thrombocytosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on July 20, 2014