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Efficacy and Safety of GS-6624 in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01369498
First received: June 6, 2011
Last updated: October 22, 2014
Last verified: October 2014
  Purpose

This study is to evaluate the efficacy and safety of GS-6624 on bone marrow fibrosis either alone or in combination with ruxolitinib in participants with Primary myelofibrosis (PMF) and Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis (ET/PV MF).

The study is designed as a two stage trial. In the stage 1, patients will be randomized into two cohorts to receive either 200 or 700 mg of study drug. In the stage 2, patients on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.


Condition Intervention Phase
Myelofibrosis
Drug: GS-6624
Drug: Ruxolitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Evaluate the Efficacy and Safety of GS-6624 in Adult Subjects With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Rate of clinical response as defined by reduction in bone marrow fibrosis score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of clinical response as defined by improvement in hemoglobin, platelet, or absolute neutrophil count [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Change in Myelofibrosis Symptoms Assessment Score [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Changes in cytokine levels [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Anti-GS-6624 antibody formation [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: June 2011
Study Completion Date: September 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GS-6624 200 mg
Participants in stage 1 of study will receive GS-6624 200 mg for up to 28 weeks.
Drug: GS-6624
GS-6624 200 mg or 700 mg administered intravenously over approximately 30 minutes every 2 weeks
Other Name: AB0024
Experimental: GS-6624 700 mg
Participants in stage 1 of study will receive GS-6624 700 mg for up to 28 weeks.
Drug: GS-6624
GS-6624 200 mg or 700 mg administered intravenously over approximately 30 minutes every 2 weeks
Other Name: AB0024
Experimental: GS-6624 200 mg+ruxolitinib
In stage 2, participants on stable doses of ruxolitinib will receive GS-6624 200 mg for at least 24 weeks.
Drug: GS-6624
GS-6624 200 mg or 700 mg administered intravenously over approximately 30 minutes every 2 weeks
Other Name: AB0024
Drug: Ruxolitinib
In stage 2, participants will be on a stable dose of ruxolitinib and will continue their treatment in combination with GS-6624
Experimental: GS-6624 700 mg+ruxolitinib
In stage 2, participants on stable doses of ruxolitinib will receive GS-6624 700 mg for at least 24 weeks.
Drug: GS-6624
GS-6624 200 mg or 700 mg administered intravenously over approximately 30 minutes every 2 weeks
Other Name: AB0024
Drug: Ruxolitinib
In stage 2, participants will be on a stable dose of ruxolitinib and will continue their treatment in combination with GS-6624

  Eligibility

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

Inclusion Criteria:

  • Must be diagnosed with PMF or post ET/PV MF with intermediate-1, intermediate-2 or high risk disease according to the IWG prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is ≥ 10 cm below left costal margin by physical exam.
  • Must have adequate organ function as demonstrated by the following:
  • ALT (SGPT) and/or AST (SGOT) ≤ 2.5x upper limit of normal (ULN), or ≤ 4x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
  • Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
  • Serum creatinine ≤ 2.5 mg/dL. 2.5 mg/dL.
  • In Stage 2, subjects must be on ruxolitinib for at least 8 weeks and on a stable dose for at least 4 weeks.
  • ECOG performance status (PS) ≤ 2
  • Treatment-related toxicities from prior therapies must have resolved to Grade ≤ 1
  • Women of childbearing potential and men must agree to using one medically approved (ie, mechanical or pharmacological) contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug. Please refer to Section 11 for a definition of female of child bearing potential and a list of acceptable contraceptive methods for this study.

Exclusion Criteria:

  • Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Pregnant or lactating.
  • Known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
  • History or presence of any form of cancer within the 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
  • Participation in an investigational drug or device trial within 2 weeks prior to study Day 1 or within 5 times the half-life of the investigational agent in the other clinical study, if known.
  • Use of any cytotoxic chemotherapeutic agents (eg, hydroxyurea), corticosteroids (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immune modulators (eg, thalidomide) within 2 weeks and interferon use within 4 weeks prior to study Day 1.
  • Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
  • History of surgery within 2 weeks prior to enrollment or anticipated surgery during the study period.
  • Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent.
  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: NCT01369498

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
University of California San Diego
San Diego, California, United States
Stanford University Medical center
Stanford, California, United States, 94305
United States, Missouri
Washington University in St. Louis
St. Louis, Missouri, United States, 63110
United States, Ohio
Oncology Hematology Care Clinical Trials
Cincinnati, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Utah University
Salt Lake City, Utah, United States
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Zung Thai, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01369498     History of Changes
Obsolete Identifiers: NCT01242709
Other Study ID Numbers: AB0024-102
Study First Received: June 6, 2011
Last Updated: October 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hematology
Myelofibrosis
Thrombocythemia Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Blood Diseases
Leukemia
Blood Disorders

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

ClinicalTrials.gov processed this record on November 25, 2014