Clinical Trials /

A Phase 2 Study Of PRM-151 In Participants With Myelofibrosis

NCT01981850

Description:

PRM-151 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. The purpose of this study is to gather information on whether PRM-151 has an effect on the MF disease, whether it is safe in patients with MF, and how well it is tolerated.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study Of PRM-151 In Participants With Myelofibrosis
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: BO42355
  • SECONDARY ID: PRM-151G-101
  • SECONDARY ID: 2015-001718-80
  • NCT ID: NCT01981850

Conditions

  • Primary Myelofibrosis
  • Polycythemia Vera
  • Post-Essential Thrombocythemia Myelofibrosis

Interventions

DrugSynonymsArms
PRM-151recombinant human pentraxin-2Stage 1: Cohort 1 Every 4 Weeks
RuxolitinibJakafiStage 1: Cohort 2 Every 4 Weeks

Purpose

PRM-151 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. The purpose of this study is to gather information on whether PRM-151 has an effect on the MF disease, whether it is safe in patients with MF, and how well it is tolerated.

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 PRM-151 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 PRM-151 or PRM-151 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 PRM-151 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 PRM-151. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Stage 1: Cohort 1 WeeklyExperimentalParticipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent PRM-151 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.
  • PRM-151
Stage 1: Cohort 1 Every 4 WeeksExperimentalParicipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent PRM-151 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.
  • PRM-151
Stage 1: Cohort 2 WeeklyExperimentalParticipants 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 PRM-151 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.
  • PRM-151
  • Ruxolitinib
Stage 1: Cohort 2 Every 4 WeeksExperimentalParticipants 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 PRM-151 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.
  • PRM-151
  • Ruxolitinib
Stage 2: Cohort 1 0.3mg/kg Every 4 WeeksExperimentalParticipants will be treated with single agent PRM-151 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.
  • PRM-151
Stage 2: Cohort 2 3mg/kg Every 4 WeeksExperimentalParticipants will be treated with single agent PRM-151 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.
  • PRM-151
Stage 2: Cohort 3 10mg /kg Every 4 WeeksExperimentalParticipants will be treated with single agent PRM-151 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.
  • PRM-151

Eligibility Criteria

        Inclusion Criteria:

          1. Participants must be ≥18 years of age at the time of signing the Informed Consent Form
             (ICF);

          2. Participants must voluntarily sign an ICF;

          3. Participants must have a pathologically confirmed diagnosis of PMF as per the WHO
             diagnostic criteria or post ET/PV MF;

          4. At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;

          5. Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT
             Dynamic International Prognostic Scoring System

          6. A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1
             treatment to establish the baseline fibrosis score;

          7. Participants must not be candidates for ruxolitinib based on EITHER:

               1. Platelet count < 50 x 10e9/L, OR

               2. 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;

          8. Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status
             of 0-2. (Appendix F);

          9. Life expectancy of at least twelve months;

         10. 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;

         11. Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments,
             excluding alopecia;

         12. 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.

         13. Ability to adhere to the study visit schedule and all protocol requirements;

         14. 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.

        Exclusion Criteria:

          1. White blood cell count > 25 x 10e9/L or > 10% peripheral blood blasts;

          2. Other invasive malignancies within the last 3 years, except non- melanoma skin cancer
             and localized cured prostate and cervical cancer;

          3. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia
             requiring medication or mechanical control within the last 6 months;

          4. Presence of active serious infection;

          5. 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;

          6. Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B,
             or C infection;

          7. Organ transplant recipients other than bone marrow transplant;

          8. Women who are pregnant or lactating.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Stage 1: Overall Response Rate (ORR)
Time Frame:Up until and including completion of 6 cycles (each cycle is 28 days)
Safety Issue:
Description:ORR is defined as the percent of participants with a response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. This is defined as those participants who achieve clinical improvement (CI), partial remission (PR), or complete remission (CR) at a post-baseline assessment of treatment response OR have 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.

Secondary Outcome Measures

Measure:Stage 1: Bone Marrow Myelofibrosis (MF) Grade Shifts
Time Frame:Baseline, Weeks 12 and 24
Safety Issue:
Description:Change in Bone Marrow Fibrosis According to European Consensus on Grading of Bone Marrow Fibrosis
Measure:Stage 1: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes
Time Frame:Baseline, beginning of each cycle (Cycle 2 onward). A cycle is 28 days.
Safety Issue:
Description:
Measure:Stage 2: Bone Marrow Response Rate
Time Frame:Up until and including completion of 9 cycles (each cycle is 28 days)
Safety Issue:
Description:
Measure:Stage 2: Bone Marrow (BM) Response Rate (MF Grade) at Each Visit
Time Frame:Day 1 on Cycles 2, 3, 4, 5, 6, 7, 8, 9 (28 day length cycles) and Cycle 9 Day 29
Safety Issue:
Description:
Measure:Stage 2: Duration of Bone Marrow Response
Time Frame:From first decrease from baseline of one grade to time of return to baseline levels
Safety Issue:
Description:
Measure:Stage 2: Hemoglobin Improvement
Time Frame:Up until and including completion of 9 cycles (each cycle is 28 days)
Safety Issue:
Description:As measured by percent of participants with : Red cell transfusion independence (no transfusions for ≥ 12 consecutive weeks) OR 50% reduction in 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 is dependent on baseline hemoglobin/transfusion status)
Measure:Stage 2: Platelet Improvement
Time Frame:Up until and including completion of 9 cycles (each cycle is 28 days)
Safety Issue:
Description:Percent of participants with: Platelet transfusion independence (no transfusions for ≥ 12 consecutive weeks) OR 50% reduction in platelets transfusions for ≥ 12 consecutive weeks OR Percent of participants with: 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 Percent of participants with: 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)
Measure:Stage 2: Symptom Improvement
Time Frame:Up until and including completion of 9 cycles (each cycle is 28 days)
Safety Issue:
Description:Percent of participants with 50% reduction in MPN-SAF TSS from baseline over time
Measure:Stage 2: Percent of Participants with Complete Response, Partial Response, Clinical Improvement, Stable Disease, and Progressive Disease According to IWG-MRT Criteria
Time Frame:Up until and including completion of 9 cycles (each cycle is 28 days)
Safety Issue:
Description:
Measure:OLE: Secondary Endpoints as per the Analyses of the Main Phases in Stage 1 or Stage 2
Time Frame:From cycle 7 (Stage 1) or cycle 10 (Stage 2) every third cycle (every 3 months) until study discontinuation. Each cycle is 28 days.
Safety Issue:
Description:When applicable

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • fibrosis

Last Updated

November 24, 2020