MyelofibrosisPhase 2NCT01369498

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

A Phase 2 study testing Simtuzumab and Ruxolitinib in people with Myelofibrosis, run by Gilead Sciences at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Myelofibrosis
What is being tested?: Simtuzumab and Ruxolitinib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 54 participants
Where: 7 sitesUnited States
Study dates: 30 Jun 2011to 24 Sep 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 9Show fewer

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.

Who cannot join

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.

Show all 9Show fewer

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.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Oncology Hematology Care Clinical Trials
Cincinnati, Ohio
Cleveland Clinic
Cleveland, Ohio
MD Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology
Nashville, Tennessee
Mayo Clinic
Scottsdale, Arizona, 85259
Washington University in St. Louis
St Louis, Missouri, 63110
Stanford University Medical center
Stanford, California, 94305

Other trials in United States

About this study

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

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.

Conditions: Myelofibrosis
Being tested: Simtuzumab, Ruxolitinib
Keywords: Hematology, Myelofibrosis, Thrombocythemia Myelofibrosis, Bone Marrow Diseases, Hematologic Diseases, Blood Diseases, Leukemia, Blood Disorders
Medical subject headings: Primary Myelofibrosis, Bone Marrow Diseases, Hematologic Diseases, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SimtuzumabDrug
Also called GS-6624, AB0024
Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
RuxolitinibDrug
In Stage 2, participants will be on a stable dose of ruxolitinib

Study groups in NCT01369498
Study group	Role	What they receive
Simtuzumab 200 mg	Experimental	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. Receives: Drug: Simtuzumab
Simtuzumab 700 mg	Experimental	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. Receives: Drug: Simtuzumab
Simtuzumab 200 mg+Ruxolitinib	Experimental	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. Receives: Drug: Simtuzumab; Drug: Ruxolitinib
Simtuzumab 700 mg+Ruxolitinib	Experimental	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. Receives: Drug: Simtuzumab; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC)
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).
Measured: Baseline; Weeks 12, 24 and any time post baseline (enrollment up to 94 weeks)
Percentage of Participants With Adverse Events (AEs)
Measured: First dose date up to the last dose date (maximum: 94 weeks) plus 28 days
Change From Baseline in Myelofibrosis Symptoms Assessment Score
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.
Measured: Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks)
Change From Baseline in Cytokine Levels
Biomarker samples were collected to evaluate the effects of SIM treatment on markers of serum and plasma cytokines.
Measured: Baseline; Week 24
Percentage of Participants With Anti-Simtuzumab Antibody Formation
Blood samples were collected for the presence of anti-SIM antibodies which was determined using a validated electro-chemiluminescent (ECL) assay screening test.
Measured: Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jun 201124 Sep 2014

First posted9 Jun 2011 (estimated)
Study start30 Jun 2011
Primary completion5 Jun 2014
Study completion24 Sep 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for MyelofibrosisStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 54 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01369498
Sponsor's protocol ID: AB0024-102
Status last verified: Jun 2020
First submitted: 6 Jun 2011
Last updated: 1 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)
RecruitingPhase 3
A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib
Myelofibrosis, Anemia
RecruitingObservational study
Motor Development and Early Predictors of Psychomotor Outcomes in Preterm and Term Infants Assessed by MOS-R and Caregiver Questionnaire at 18 and 36 Months
Neurodevelopmental Disorders, Motor Skills Disorders
Active, not recruitingPhase 3
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
Myelofibrosis
RecruitingPhase 2
Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
Primary Myelofibrosis, Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

All Myelofibrosis trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01369498
Acronym / sponsor ID: AB0024-102
Conditions: Myelofibrosis
Keywords: Hematology, Myelofibrosis, Thrombocythemia Myelofibrosis, Bone Marrow Diseases, Hematologic Diseases, Blood Diseases, Leukemia, Blood Disorders
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 54 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 30 Jun 2011 (actual)
Primary completion: 5 Jun 2014 (actual)
Study completion: 24 Sep 2014 (actual)
First posted: 9 Jun 2011 (estimated)
Results: Posted 1 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Simtuzumab 200 mg	Experimental	Drug: SimtuzumabParticipants 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.
Simtuzumab 700 mg	Experimental	Drug: SimtuzumabParticipants 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.
Simtuzumab 200 mg+Ruxolitinib	Experimental	Drug: Simtuzumab, Drug: RuxolitinibIn 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.
Simtuzumab 700 mg+Ruxolitinib	Experimental	Drug: Simtuzumab, Drug: RuxolitinibIn 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SimtuzumabAlso: GS-6624, AB0024Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks	Drug	Simtuzumab 200 mg, Simtuzumab 200 mg+Ruxolitinib, Simtuzumab 700 mg, Simtuzumab 700 mg+Ruxolitinib
RuxolitinibIn Stage 2, participants will be on a stable dose of ruxolitinib	Drug	Simtuzumab 200 mg+Ruxolitinib, Simtuzumab 700 mg+Ruxolitinib

Primary outcome

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.

5 secondary outcomes

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)
Percentage of Participants With Adverse Events (AEs)
Time frame: First dose date up to the last dose date (maximum: 94 weeks) plus 28 days
Change From Baseline in Myelofibrosis Symptoms Assessment Score
Time frame: Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks)
Change From Baseline in Cytokine Levels
Time frame: Baseline; Week 24
Percentage of Participants With Anti-Simtuzumab Antibody Formation
Time frame: Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks)

Results and safety

Results posted to the registry on 1 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Stage 1: SIM 200 mg	12	0
Stage 1: SIM 700 mg	12	0
Stage 2: SIM 200 mg+Ruxolitinib	15	0
Stage 2: SIM 700 mg+Ruxolitinib	15	0

Primary outcome: 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. Number (90% Confidence Interval). Unit: percentage of participants

Measure	Stage 1: SIM 200 mg n = 11	Stage 1: SIM 700 mg n = 12	Stage 2: SIM 200 mg+Ruxolitinib n = 15	Stage 2: SIM 700 mg+Ruxolitinib n = 15
Value	0 (0.0 to 23.8)	16.7 (3.0 to 43.8)	6.7 (0.3 to 27.9)	13.3 (2.4 to 36.3)

Population analysed: 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.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose date up to the last dose date (maximum: 94 weeks) plus 28 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stage 1: SIM 200 mg	8 of 12 (66.7%)	12 of 12 (100%)	0 of 12
Stage 1: SIM 700 mg	1 of 12 (8.3%)	12 of 12 (100%)	1 of 12
Stage 2: SIM 200 mg+Ruxolitinib	5 of 15 (33.3%)	15 of 15 (100%)	1 of 15
Stage 2: SIM 700 mg+Ruxolitinib	4 of 15 (26.7%)	15 of 15 (100%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Myelofibrosis

RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)
RecruitingPhase 3
A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib
Myelofibrosis, Anemia
RecruitingObservational study
Motor Development and Early Predictors of Psychomotor Outcomes in Preterm and Term Infants Assessed by MOS-R and Caregiver Questionnaire at 18 and 36 Months
Neurodevelopmental Disorders, Motor Skills Disorders
Active, not recruitingPhase 3
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
Myelofibrosis
RecruitingPhase 2
Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
Primary Myelofibrosis, Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Simtuzumab and Ruxolitinib in people with Myelofibrosis, run by Gilead Sciences at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Baseline; Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01369498.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2020.