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

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ClinicalTrials.gov Identifier: NCT01369498
Recruitment Status : Completed
First Posted : June 9, 2011
Results First Posted : July 1, 2020
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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.


Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: Simtuzumab Drug: Ruxolitinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : June 30, 2011
Actual Primary Completion Date : June 5, 2014
Actual Study Completion Date : September 24, 2014


Arm Intervention/treatment
Experimental: Simtuzumab 200 mg
Participants in Stage 1 of study will receive simtuzumab 200 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.
Drug: Simtuzumab
Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
Other Names:
  • GS-6624
  • AB0024

Experimental: Simtuzumab 700 mg
Participants in Stage 1 of study will receive simtuzumab 700 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.
Drug: Simtuzumab
Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
Other Names:
  • GS-6624
  • AB0024

Experimental: Simtuzumab 200 mg+Ruxolitinib
In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 200 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.
Drug: Simtuzumab
Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
Other Names:
  • GS-6624
  • AB0024

Drug: Ruxolitinib
In Stage 2, participants will be on a stable dose of ruxolitinib

Experimental: Simtuzumab 700 mg+Ruxolitinib
In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 700 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.
Drug: Simtuzumab
Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
Other Names:
  • GS-6624
  • AB0024

Drug: Ruxolitinib
In Stage 2, participants will be on a stable dose of ruxolitinib




Primary Outcome Measures :
  1. Rate of Clinical Response as Defined by the Percentage of Participants With Reduction at Week 24 From Baseline in the Bone Marrow Fibrosis Score [ Time Frame: Baseline; Week 24 ]
    Overall response for the study drug is defined by the reduction in bone marrow fibrosis score which is on a scale of 0-3 where 0 indicates the scattered linear reticulin with no fiber intersections representing normal marrow and 3 indicates dense increase in reticulin fibrosis with fiber intersections, often with osteosclerosis. Reduction from baseline of score indicates improvement in clinical condition.


Secondary Outcome Measures :
  1. Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC) [ Time Frame: Baseline; Weeks 12, 24 and any time post baseline (enrollment up to 94 weeks) ]
    Overall response for the study drug was defined by the rate of clinical improvement in hemoglobin, platelet or ANC. Clinical improvement in hemoglobin was defined as a ≥ 2 g/dL increase from baseline in hemoglobin level and transfusion independent (absence of red blood cell (RBC) transfusions in prior 8 weeks and applicable only for participants with baseline hemoglobin level of < 10 g/dL); clinical improvement in platelets was defined as a ≥ 100% increase from baseline in platelet count and an absolute platelet count of ≥ 50 x 10^9/L (applicable only for participants with baseline platelet count < 50 x 10^9/L); clinical improvement in ANC is defined as a ≥ 100% increase from baseline in ANC and an ANC of ≥ 0.5 x 10^9/L (applicable only for participants with baseline ANC < 1 x 10^9/L).

  2. Percentage of Participants With Adverse Events (AEs) [ Time Frame: First dose date up to the last dose date (maximum: 94 weeks) plus 28 days ]
  3. Change From Baseline in Myelofibrosis Symptoms Assessment Score [ Time Frame: Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks) ]
    Myelofibrosis symptom assessment was performed using myeloproliferative neoplasm symptoms assessment form (MPN-SAF) which is a 27-item questionnaire to address symptom burden and quality of life. The form consists of 27 questions which are scored on a scale of 0-10 by participants based on how symptoms are affecting them, where 0 indicates less symptoms while 10 indicated more severe symptoms and greater inactivity. The MPN-SAF score was calculated at each visit for each participant as an average of the scales for each question and all answered questions. If the number of questions not answered at 1 visit was > 10, then the MPN-SAF score for that visit was taken as missing. A negative change from Baseline indicated improvement.

  4. Change From Baseline in Cytokine Levels [ Time Frame: Baseline; Week 24 ]
    Biomarker samples were collected to evaluate the effects of SIM treatment on markers of serum and plasma cytokines.

  5. Percentage of Participants With Anti-Simtuzumab Antibody Formation [ Time Frame: Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks) ]
    Blood samples were collected for the presence of anti-SIM antibodies which was determined using a validated electro-chemiluminescent (ECL) assay screening test.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01369498


Locations
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United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
Stanford University Medical center
Stanford, California, United States, 94305
United States, Missouri
Washington University in St. Louis
Saint 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
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01369498    
Obsolete Identifiers: NCT01242709
Other Study ID Numbers: AB0024-102
First Posted: June 9, 2011    Key Record Dates
Results First Posted: July 1, 2020
Last Update Posted: July 1, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
Hematology
Myelofibrosis
Thrombocythemia Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Blood Diseases
Leukemia
Blood Disorders
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders