Clinical trial NCT01369498: Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelofibrosis
Keywords: Hematology
Myelofibrosis
Thrombocythemia Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Blood Diseases
Leukemia
Blood Disorders
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-06-09
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the efficacy and safety of simtuzumab (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, participants will be randomized into two cohorts to receive either 200 or 700 mg of study drug. In the stage 2, participants on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.


Eligibility 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 international working group (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:
* Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 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.
* In Stage 2, participants must be on ruxolitinib for at least 8 weeks and on a stable dose for at least 4 weeks.
* Eastern cooperative oncology group (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. Definition of female of child bearing potential and a list of acceptable contraceptive methods for this study applies per protocol.

Exclusion Criteria:

* Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the participant from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the participant 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.

Primary outcomes:
measure: Rate of Clinical Response as Defined by the Percentage of Participants With Reduction at Week 24 From Baseline in the Bone Marrow Fibrosis Score
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC)
timeFrame: Baseline; Weeks 12, 24 and any time post baseline (enrollment up to 94 weeks)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: First dose date up to the last dose date (maximum: 94 weeks) plus 28 days
measure: Change From Baseline in Myelofibrosis Symptoms Assessment Score
timeFrame: Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks)
measure: Change From Baseline in Cytokine Levels
timeFrame: Baseline; Week 24
measure: Percentage of Participants With Anti-Simtuzumab Antibody Formation
timeFrame: Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Stanford
country: United States
facility: Stanford University Medical center
state: California
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: