Primary MyelofibrosisPhase 2NCT01981850

A Phase 2 Study of RO7490677 In Participants With Myelofibrosis

A Phase 2 study testing RO7490677 and Ruxolitinib in people with Primary Myelofibrosis and Polycythemia Vera, run by Hoffmann-La Roche at 23 sites in 8 countries.

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

RO7490677 is an investigational drug that is being developed for possible use in the treatment of myelofibrosis (MF), a disease in which the bone marrow, which is the organ in the body that makes blood cells, is replaced by fibrosis, or excess scar tissue. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Primary Myelofibrosis, Polycythemia Vera, Post-Essential Thrombocythemia Myelofibrosis
What is being tested?: RO7490677 and Ruxolitinib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 125 participants
Where: 23 sitesin 8 countries
Study dates: 1 Oct 2013to 10 Jul 2020
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

Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
Participants must voluntarily sign an ICF;
Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score;

Show all 19Show fewer

Participants must not be candidates for ruxolitinib based on EITHER:
Platelet count < 50 x 10e9/L, OR
Hgb < 100 g/L, have received ≥ 2 units PRBC in the 12 weeks prior to study entry, and be intolerant of or had inadequate response to ruxolitinib;
Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. (Appendix F);
Life expectancy of at least twelve months;
At least four weeks must have elapsed between the last dose of any MF- directed drug treatments for myelofibrosis (including investigational therapies) and study enrollment;
Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia;
Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if >55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are outlined in the protocol.
Ability to adhere to the study visit schedule and all protocol requirements;
Must have adequate organ function as demonstrated by the following:
ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN), or ≤ 4 x 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 EMH related to MF);
Serum creatinine ≤ 2.5 mg/dL x ULN.

Who cannot join

White blood cell count > 25 x 10e9/L or > 10% peripheral blood blasts;
Other invasive malignancies within the last 3 years, except non- melanoma skin cancer and localized cured prostate and cervical cancer;
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months;
Presence of active serious infection;
Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) 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;
Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection;
Organ transplant recipients other than bone marrow transplant;
Women who are pregnant or lactating.

Trial locations and contacts

23 sites in 8 countries.

Country

City, postcode or hospital

23 sites in 8 countries

United States11 sites

University of Michigan
Ann Arbor, Michigan, 48109-2800
Emory Hospital
Atlanta, Georgia, 30322
University of Maryland Medical Center
Baltimore, Maryland, 21201
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
MD Anderson Cancer Center
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Mount Sinai Medical Center
New York, New York, 10029
Weill Cornell Medical Center
New York, New York, 10065
Stanford Cancer Institute
Palo Alto, California, 94304
Mayo Clinic Cancer Center
Phoenix, Arizona, 85054
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157

Other trials in United States

Canada2 sites

The Princess Margaret Cancer Centre
Toronto, Ontario, M5T 2M9
Providence Health Care
Vancouver, British Columbia, V6Z 2A5

Other trials in Canada

Germany2 sites

University Medical Center RWTH Aachen
Aachen, D-52074
Johannes Wesling Academic Medical Center
Minden, 32429

Other trials in Germany

Israel2 sites

Hadassah Medical Centre
Jerusalem, 91120
Meir Medical Centre
Kfar Saba, 4428164

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Italy2 sites

Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Marche Nord Hospital
Pesaro, 61122

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Netherlands2 sites

Radboud University Medical Center
Nijmegen, 6525 GA
Erasmus Medical Center
Rotterdam, South Holland, 3015 CE

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France1 site

Hospital Saint-Louis
Paris, 75475

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United Kingdom1 site

Guy's and St. Thomas' Hospital
London

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About this study

Official title: A Phase 2, Prospective Study Of PRM-151 In Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV MF), Or Post-Essential Thrombocythemia MF (Post-ET MF)

The purpose of this study is to gather information on whether RO7490677 has an effect on the MF disease, whether it is safe in patients with MF, and how well it is tolerated.

Read the detailed description

Stage 1 of this study has completed. Stage 1 was an open-label, Simon two stage, Phase 2 study to determine the efficacy and safety of two different dose schedules of RO7490677 in participants with PMF and post ET/PV MF. There were two treatment cohorts, each assigned to one of two dose schedules receiving either single-agent RO7490677 or RO7490677 in combination with ruxolitinib. Participants were assigned to a weekly or every four week dosing schedule by the investigator.

Stage 2 is a randomized, double-blind Phase 2 study to determine the efficacy and safety of three different doses of RO7490677 in participants with PMF and post ET/PV MF. Participants will be randomized to one of three doses: 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg of RO7490677. This is the second stage of an adaptive design study as defined in FDA Draft Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics, February 2010. Modifications to dose levels, schedule, and regimen have been made in Stage 2 based on data from Stage 1.

Conditions: Primary Myelofibrosis, Polycythemia Vera, Post-Essential Thrombocythemia Myelofibrosis
Being tested: RO7490677, Ruxolitinib
Keywords: fibrosis
Medical subject headings: Primary Myelofibrosis, Polycythemia Vera, Fibrosis

What participants receive

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

RO7490677Biological
Also called originally called PRM-151, and also known as rhPTX-2
IV infusion
RuxolitinibDrug
Also called Jakafi
IV infusion

Study groups in NCT01981850
Study group	Role	What they receive
Stage 1: Cohort 1 Weekly	Experimental	Participants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg IV on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Receives: Biological: RO7490677
Stage 1: Cohort 1 Every 4 Weeks	Experimental	Paricipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Receives: Biological: RO7490677
Stage 1: Cohort 2 Weekly	Experimental	Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Receives: Biological: RO7490677; Drug: Ruxolitinib
Stage 1: Cohort 2 Every 4 Weeks	Experimental	Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Receives: Biological: RO7490677; Drug: Ruxolitinib
Stage 2: Cohort 1 0.3mg/kg Every 4 Weeks	Experimental	Participants will be treated with single agent RO7490677 at a dose of 0.3 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Receives: Biological: RO7490677
Stage 2: Cohort 2 3mg/kg Every 4 Weeks	Experimental	Participants will be treated with single agent RO7490677 at a dose of 3.0 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Receives: Biological: RO7490677
Stage 2: Cohort 3 10mg /kg Every 4 Weeks	Experimental	Participants will be treated with single agent RO7490677 at a dose of 10 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Receives: Biological: RO7490677

What is being measured

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

Stage 1 Main Phase: Overall Response Rate (ORR)
ORR was defined as the percent of participants with a response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. This was defined as those participants who achieved clinical improvement (CI), partial remission (PR), or complete remission (CR) at a post-baseline assessment of treatment response OR had at least stable disease (SD) for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease.
Measured: Up until and including completion of 6 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Bone Marrow Response Rate (BMRR)
Response rate was defined as the percent of participants with a reduction in bone marrow fibrosis by at least one grade according to World Health Organization (WHO) criteria from baseline to any time during the study. This was determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy.
Measured: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 1 Main + Open-Label Extension (OLE): ORR
ORR was defined as the percent of participants with a response according to the IWG-MRT criteria. This was defined as those participants who achieved CI, PR, or CR at a post-baseline assessment of treatment response OR had at least SD for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease. Participants who achieved a clinical benefit in the main phase had the opportunity to remain on treatment. The determination of ORR in the main phase is outlined in the arms description below. Participants who didn't achieve a benefit had the opportunity to switch to a different dosing schedule in the OLE phase. The determination of ORR in the OLE phase is outlined in the arms descriptions below.
Measured: From cycle 1 day 1 up until cycle 6, day 29 (Main Phase). From cycle 7 day 1 up until study discontinuation or study termination, up to 83 cycles (OLE). Each cycle is 28 days.
Stage 2 Main + Open-Label Extension (OLE): BMRR
Defined as the percent of participants with a reduction in bone marrow fibrosis score by at least one grade according to WHO criteria at any time during the study. As determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy. Participants in the main phase had the opportunity to remain on treatment (as outlined in the arms description below). Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment and receive PRM-151 10 mg/kg/Q4W (as outlined in the arms description below).
Measured: From cycle 1 day 1 up until cycle 9 day 29 (main phase). From cycle 10 day 1 up until study discontinuation or study termination, up to 51 cycles (OLE). Each cycle is 28 days.

Secondary outcomes (9)

Stage 1 Main Phase: BMRR
Bone marrow response was defined as a reduction in bone marrow fibrosis score by at least one grade from baseline at anytime during the study.
Measured: Baseline, Weeks 12 and 24
Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes
The MPN-SAF TSS total symptom score was the sum of the following 10 items: Filling up quickly when you eat (early satiety), abdominal discomfort, inactivity, Problems with concentration, Worst fatigue, Night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months. The MPN-SAF Total Symptom Score had a possible range of 0 to 100, where a lower score was more favorable. The values reported are the change from baseline scores.
Measured: Baseline, beginning of each cycle (Cycle 2 onward). Each cycle is 28 days.
Stage 2 Main Phase: BMRR
Response rate was defined as the percent of participants with a reduction in bone marrow fibrosis by at least one grade according to World Health Organization (WHO) criteria at any time during the study. This was determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy.
Measured: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: BMRR - Reduction of Bone Marrow Fibrosis by Visit
Reduction in bone marrow fibrosis score: Reduction of at least one grade from baseline. Bone marrow fibrosis grades according to WHO criteria (as determined by central adjudication).
Measured: Day 1 on Cycles 4, 7, 10 and Cycle 9 Day 29. Each cycle is 28 days.
Stage 2 Main Phase: Duration of Bone Marrow Improvement
Duration of response was defined as time from first decrease from baseline >= 1 grade to time of return to baseline levels.
Measured: From first decrease from baseline of one grade to time of return to baseline levels, up to cycle 9 of 28-day cycles.
Stage 2 Main Phase: Hemoglobin Improvement
Hemoglobin improvement was measured by the percent of participants with: Red cell transfusion independence (no transfusions for >= 12 consecutive weeks) OR 50% reduction in red blood cell (RBC) transfusions for >= 12 consecutive weeks OR percent of participants with >= 10 g/L and >= 20 g/L increase in hemoglobin for >= 12 consecutive weeks without transfusions (outcome parameter assessed was dependent on baseline hemoglobin/transfusion status).
Measured: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Platelet Improvement
Platelet improvement was measured by the percent of participants with: Platelet transfusion independence (no transfusions for >= 12 consecutive weeks) OR 50% reduction in platelets transfusions for >= 12 consecutive weeks OR doubling of baseline platelet count for >= 12 consecutive weeks without platelet transfusions OR platelet count > 50 x 10e9/L for >=12 consecutive weeks without platelet transfusions OR doubling of baseline platelet count for >= 12 consecutive weeks without platelet transfusions OR platelet count > 25 x 10e9/L for >= 12 consecutive weeks without platelet transfusions (outcome parameter assessed is dependent on baseline platelet status).
Measured: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Symptom Improvement
Symptom improvement was assessed as the percent of participants with 50% reduction in MPN-SAF TSS from baseline over time. The MPN-SAF TSS total symptom score was the sum of the following 10 items: Filling up quickly when you eat (early satiety), abdominal discomfort, inactivity, Problems with concentration, Worst fatigue, Night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months. The MPN-SAF Total Symptom Score had a possible range of 0 to 100, where a lower score was more favorable.
Measured: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Percentage of Participants With Complete Response (CR), Partial Response (PR), Clinical Improvement (CI), Stable Disease (SD), and Progressive Disease (PD) According to IWG-MRT Criteria
Best Overall Response: (CR, PR, CI), SD and PD according to the IWG-MRT Criteria.
Measured: Up until and including completion of 9 cycles. Each cycle is 28 days.

Timeline

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

1 Oct 201310 Jul 2020

First posted13 Nov 2013 (estimated)
Study start1 Oct 2013
Primary completion10 Jul 2020
Study completion10 Jul 2020

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary MyelofibrosisStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe 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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 125 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01981850
Sponsor's protocol ID: BO42355
Other IDs: PRM-151G-101, 2015-001718-80, 2015
Status last verified: Dec 2021
First submitted: 29 Oct 2013
Last updated: 5 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Publications

Verstovsek S, Foltz L, Gupta V, Hasserjian R, Manshouri T, Mascarenhas J, Mesa R, Pozdnyakova O, Ritchie E, Veletic I, Gamel K, Hamidi H, Han L, Higgins B, Trunzer K, Uguen M, Wang D, El-Galaly TC, Todorov B, Gotlib J. Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial. Haematologica. 2023 Oct 1;108(10):2730-2742. doi: 10.3324/haematol.2022.282411.
PubMed 37165840

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
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
Not yet recruitingPhase 1
Maintenance Treatment With Imetelstat in Patients With High-Risk Myeloid Neoplasms After Allo-SCT
High-risk Myeloid Malignancy, Allogenic Stem Cell Transplantation

All Primary Myelofibrosis trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Prospective Study Of PRM-151 In Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV MF), Or Post-Essential Thrombocythemia MF (Post-ET MF)
ClinicalTrials.gov ID: NCT01981850
Acronym / sponsor ID: BO42355
Conditions: Primary Myelofibrosis, Polycythemia Vera, Post-Essential Thrombocythemia Myelofibrosis
Keywords: fibrosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 125 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 1 Oct 2013 (actual)
Primary completion: 10 Jul 2020 (actual)
Study completion: 10 Jul 2020 (actual)
First posted: 13 Nov 2013 (estimated)
Results: Posted 5 Jan 2022

Clinical summary

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

The purpose of this study is to gather information on whether RO7490677 has an effect on the MF disease, whether it is safe in patients with MF, and how well it is tolerated.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 7

Arm	Type	Receives
Stage 1: Cohort 1 Weekly	Experimental	Biological: RO7490677Participants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg IV on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Stage 1: Cohort 1 Every 4 Weeks	Experimental	Biological: RO7490677Paricipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Stage 1: Cohort 2 Weekly	Experimental	Biological: RO7490677, Drug: RuxolitinibParticipants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Stage 1: Cohort 2 Every 4 Weeks	Experimental	Biological: RO7490677, Drug: RuxolitinibParticipants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Stage 2: Cohort 1 0.3mg/kg Every 4 Weeks	Experimental	Biological: RO7490677Participants will be treated with single agent RO7490677 at a dose of 0.3 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Stage 2: Cohort 2 3mg/kg Every 4 Weeks	Experimental	Biological: RO7490677Participants will be treated with single agent RO7490677 at a dose of 3.0 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Stage 2: Cohort 3 10mg /kg Every 4 Weeks	Experimental	Biological: RO7490677Participants will be treated with single agent RO7490677 at a dose of 10 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.

Who may qualify

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

Key inclusion criteria (19 listed)

Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
Participants must voluntarily sign an ICF;
Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System

Key exclusion criteria (8 listed)

White blood cell count > 25 x 10e9/L or > 10% peripheral blood blasts;
Other invasive malignancies within the last 3 years, except non- melanoma skin cancer and localized cured prostate and cervical cancer;
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months;
Presence of active serious infection;
Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) 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;

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
RO7490677Also: originally called PRM-151, and also known as rhPTX-2IV infusion	Biological	Stage 1: Cohort 1 Every 4 Weeks, Stage 1: Cohort 1 Weekly, Stage 1: Cohort 2 Every 4 Weeks, Stage 1: Cohort 2 Weekly, Stage 2: Cohort 1 0.3mg/kg Every 4 Weeks, Stage 2: Cohort 2 3mg/kg Every 4 Weeks, Stage 2: Cohort 3 10mg /kg Every 4 Weeks
RuxolitinibAlso: JakafiIV infusion	Drug	Stage 1: Cohort 2 Every 4 Weeks, Stage 1: Cohort 2 Weekly

Primary outcome

Stage 1 Main Phase: Overall Response Rate (ORR)
Time frame: Up until and including completion of 6 cycles. Each cycle is 28 days.
ORR was defined as the percent of participants with a response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. This was defined as those participants who achieved clinical improvement (CI), partial remission (PR), or complete remission (CR) at a post-baseline assessment of treatment response OR had at least stable disease (SD) for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease.
Stage 2 Main Phase: Bone Marrow Response Rate (BMRR)
Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.
Response rate was defined as the percent of participants with a reduction in bone marrow fibrosis by at least one grade according to World Health Organization (WHO) criteria from baseline to any time during the study. This was determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy.
Stage 1 Main + Open-Label Extension (OLE): ORR
Time frame: From cycle 1 day 1 up until cycle 6, day 29 (Main Phase). From cycle 7 day 1 up until study discontinuation or study termination, up to 83 cycles (OLE). Each cycle is 28 days.
ORR was defined as the percent of participants with a response according to the IWG-MRT criteria. This was defined as those participants who achieved CI, PR, or CR at a post-baseline assessment of treatment response OR had at least SD for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease. Participants who achieved a clinical benefit in the main phase had the opportunity to remain on treatment. The determination of ORR in the main phase is outlined in the arms description below. Participants who didn't achieve a benefit had the opportunity to switch to a different dosing schedule in the OLE phase. The determination of ORR in the OLE phase is outlined in the arms descriptions below.
Stage 2 Main + Open-Label Extension (OLE): BMRR
Time frame: From cycle 1 day 1 up until cycle 9 day 29 (main phase). From cycle 10 day 1 up until study discontinuation or study termination, up to 51 cycles (OLE). Each cycle is 28 days.
Defined as the percent of participants with a reduction in bone marrow fibrosis score by at least one grade according to WHO criteria at any time during the study. As determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy. Participants in the main phase had the opportunity to remain on treatment (as outlined in the arms description below). Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment and receive PRM-151 10 mg/kg/Q4W (as outlined in the arms description below).

9 secondary outcomes

Stage 1 Main Phase: BMRR
Time frame: Baseline, Weeks 12 and 24
Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes
Time frame: Baseline, beginning of each cycle (Cycle 2 onward). Each cycle is 28 days.
Stage 2 Main Phase: BMRR
Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: BMRR - Reduction of Bone Marrow Fibrosis by Visit
Time frame: Day 1 on Cycles 4, 7, 10 and Cycle 9 Day 29. Each cycle is 28 days.
Stage 2 Main Phase: Duration of Bone Marrow Improvement
Time frame: From first decrease from baseline of one grade to time of return to baseline levels, up to cycle 9 of 28-day cycles.
Stage 2 Main Phase: Hemoglobin Improvement
Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Platelet Improvement
Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Symptom Improvement
Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.
Stage 2 Main Phase: Percentage of Participants With Complete Response (CR), Partial Response (PR), Clinical Improvement (CI), Stable Disease (SD), and Progressive Disease (PD) According to IWG-MRT Criteria
Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.

Results and safety

Results posted to the registry on 5 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW)	8	5
Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W)	7	5
Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib	6	4
Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib	6	6
Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W	0	0
Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W	0	0
Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W	0	0
OLE Stage 1: RO7490677 10 mg/kg IV Q4W	0	0
OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib	0	0
OLE Stage 2: RO7490677 10 mg/kg IV Q4W	0	0

Primary outcome: Stage 1 Main Phase: Overall Response Rate (ORR)

Time frame: Up until and including completion of 6 cycles. Each cycle is 28 days.. Number (90% Confidence Interval). Unit: Percentage of Participants

Measure	Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) n = 8	Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) n = 7	Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib n = 6	Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib n = 6
Value	37.5 (11.11 to 71.08)	14.3 (0.73 to 52.07)	33.3 (6.28 to 72.87)	50.0 (15.32 to 84.68)

Population analysed: The all treated population included all participants who received at least one dose of RO7490667.

Primary outcome: Stage 2 Main Phase: Bone Marrow Response Rate (BMRR)

Time frame: Up until and including completion of 9 cycles. Each cycle is 28 days.. Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W n = 33	Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W n = 32	Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W n = 32
Value	30.3 (14.62 to 45.98)	31.3 (15.19 to 47.31)	25.0 (10.00 to 40.00)

Population analysed: The all treated population included all participants randomized and who received at least one administration of the drug.

Primary outcome: Stage 1 Main + Open-Label Extension (OLE): ORR

Time frame: From cycle 1 day 1 up until cycle 6, day 29 (Main Phase). From cycle 7 day 1 up until study discontinuation or study termination, up to 83 cycles (OLE). Each cycle is 28 days.. Number (90% Confidence Interval). Unit: Percentage of Participants

Measure	Main Phase Stage 1: RO7490677 10 mg/kg IV QW; OLE: RO7490677 10 mg/kg IV Q4W n = 8	Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W n = 7	Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib; OLE: RO7490677 10 mg/kg IV Q4W + Ruxo. n = 6	Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib; OLE: RO7490677 10 mg/kg IV Q4W + Ruxo. n = 6
Value	50.0 (19.29 to 80.71)	71.4 (34.13 to 94.66)	50.0 (15.32 to 84.68)	66.7 (27.13 to 93.72)

Population analysed: The all treated population (main phase + OLE) included all participants who received at least one dose of RO7490667.

Primary outcome: Stage 2 Main + Open-Label Extension (OLE): BMRR

Time frame: From cycle 1 day 1 up until cycle 9 day 29 (main phase). From cycle 10 day 1 up until study discontinuation or study termination, up to 51 cycles (OLE). Each cycle is 28 days.. Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W n = 33	Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W n = 32	Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W n = 32
Value	30.3 (14.62 to 45.98)	34.4 (17.92 to 50.83)	25.0 (10.00 to 40.00)

Population analysed: The all treated population (main phase + OLE) included all participants randomized and who received at least one administration of the drug.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up until 6.75 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW)	2 of 8 (25%)	8 of 8 (100%)	2 of 8
Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W)	1 of 7 (14.3%)	6 of 7 (85.7%)	0 of 7
Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib	2 of 6 (33.3%)	6 of 6 (100%)	1 of 6
Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W	11 of 33 (33.3%)	32 of 33 (97%)	7 of 33
Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W	14 of 32 (43.8%)	30 of 32 (93.8%)	6 of 32
Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W	14 of 32 (43.8%)	31 of 32 (96.9%)	9 of 32
OLE Stage 1: RO7490677 10 mg/kg IV Q4W	5 of 13 (38.5%)	12 of 13 (92.3%)	0 of 13
OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib	2 of 5 (40%)	5 of 5 (100%)	0 of 5
OLE Stage 2: RO7490677 10 mg/kg IV Q4W	22 of 48 (45.8%)	32 of 48 (66.7%)	7 of 48

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37165840Verstovsek S, Foltz L, Gupta V, Hasserjian R, Manshouri T, Mascarenhas J, Mesa R, Pozdnyakova O, Ritchie E, Veletic I, Gamel K, Hamidi H, Han L, Higgins B, Trunzer K, Uguen M, Wang D, El-Galaly TC, Todorov B, Gotlib J. Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial. Haematologica. 2023 Oct 1;108(10):2730-2742. doi: 10.3324/haematol.2022.282411.
Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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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.

Clinical Trials study director

Hoffmann-La Roche

23 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RO7490677 and Ruxolitinib in people with Primary Myelofibrosis and Polycythemia Vera, run by Hoffmann-La Roche at 23 sites in 8 countries.

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 19 inclusion and 8 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 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Canada, Germany, Israel, Italy and 3 more countries. 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 5 Jan 2022). 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?

Stage 1 Main Phase: Overall Response Rate (ORR) (time frame: Up until and including completion of 6 cycles. Each cycle is 28 days.). The study lists 4 primary outcomes in all. 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 NCT01981850, which also lists 1 linked publication.

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 5 Jan 2022.