Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Leukemia

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Bone Marrow Diseases

Thrombocytosis

Thrombocythemia, Essential

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

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.

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.

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.

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.

Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks

Simtuzumab

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

Ruxolitinib

Gilead Study Director

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.

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

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

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.

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).

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.

Biomarker samples were collected to evaluate the effects of SIM treatment on markers of serum and plasma cytokines.

Blood samples were collected for the presence of anti-SIM antibodies which was determined using a validated electro-chemiluminescent (ECL) assay screening test.

Gilead Sciences

The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.

Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.

Stage 1: SIM 200 mg

Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.

Stage 1: SIM 700 mg

Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.

Stage 2: SIM 200 mg+Ruxolitinib

Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.

Stage 2: SIM 700 mg+Ruxolitinib

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.

Bone Marrow Fibrosis Score

Gilead Clinical Study Information Center

The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria, and had at least 80% adherence with study drug.

Rate of Clinical Response as Defined by the Percentage of Participants With Reduction at Week 24 From Baseline in the Bone Marrow Fibrosis Score

Week 12

Week 24

Any Time Post-Baseline

Participants were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.

Participants in Per Protocol Analysis Set with available data were analyzed.

Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC)

The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug

Percentage of Participants With Adverse Events (AEs)

Baseline

Best Change from Baseline

Change from Baseline at Cycle 1 - Day 43

Change from Baseline at Cycle 1 - Day 85

Change from Baseline at Cycle 2 - Day 43

Change from Baseline at Cycle 2 - Day 85

Change from Baseline at Cycle 3 - Day 43

Change from Baseline at Cycle 3 - Day 85

Change from Baseline at Cycle 4 - Day 43

Change from Baseline at Cycle 4 - Day 85

Change from Baseline at Cycle 5 - Day 43

Change from Baseline at Cycle 5 - Day 85

Change from Baseline at Cycle 6 - Day 43

Change from Baseline at Cycle 6 - Day 85

Change from Baseline at Cycle 7 - Day 43

Change from Baseline at Cycle 7 - Day 85

Participants in the Per Protocol Analysis Set with available data were analyzed.

Spots Global Cancer Trial Database for Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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