Clinical Trials /

A Phase 2 Study Of PRM-151 In Subjects 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:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Phase 2 Study Of PRM-151 In Subjects 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: PRM-151G-101
  • NCT ID: NCT01981850

Trial Conditions

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

Trial Interventions

DrugSynonymsArms

Trial 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 2 of this study is ongoing. Stage 2 is a randomized, double-blind Phase 2 study to determine the efficacy and safety of three different doses of PRM-151 in subjects with PMF and post ET/PV MF. Subjects 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 This is the second stage of an adaptive design study as defined in FDA Draft Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics, February 2010.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.

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 subjects with PMF and post ET/PV MF. There were two treatment cohorts, each assigned to one of two dose schedules of PRM-151. Subjects were assigned to a weekly or every four week dosing schedule by the investigator.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 0.3mg/kg Every 4 WeeksExperimentalSubjects 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.
    Cohort 2 3 mg/kg Every 4 WeeksExperimentalSubjects 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
      Cohort 3 10mg /kg Every 4 WeeksExperimentalSubjects 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

        Eligibility Criteria

        Inclusion Criteria:

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

        2. Subjects must voluntarily sign an ICF;

        3. Subjects 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. Subjects 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. Subjects 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 subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject 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:Both
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Bone marrow response rate, defined as the percent of subjects with a reduction in bone marrow fibrosis score by at least one grade according to WHO criteria at any time during the study.
        Time Frame:9 months
        Safety Issue:No
        Description:As determined by a central adjudication panel of expert hematopathologists, blinded to subject, treatment, and time of biopsy

        Secondary Outcome Measures

        Measure:Comparison of primary and secondary efficacy parameters between doses
        Time Frame:9 months
        Safety Issue:No
        Description:
        Measure:Incidence of adverse events (AEs), serious adverse events (SAEs), and changes in laboratory test results
        Time Frame:up to 40 weeks
        Safety Issue:No
        Description:
        Measure:Bone marrow improvement: Bone marrow response rate at weeks 12, 24, and 36; Duration of bone marrow response
        Time Frame:9 months
        Safety Issue:No
        Description:
        Measure:Hemoglobin improvement
        Time Frame:9 months
        Safety Issue:No
        Description:As measured by Percent of subjects with : Red cell transfusion independence (no transfusions for ≥ 12 consecutive weeks) OR 50% reduction in RBC transfusions for ≥ 12 consecutive weeks OR Percent of subjects 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:Platelet improvement
        Time Frame:9 months
        Safety Issue:No
        Description:Percent of subjects with: Platelet transfusion independence (no transfusions for ≥ 12 consecutive weeks) OR 50% reduction in platelets transfusions for ≥ 12 consecutive weeks OR Percent of subjects 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 subjects 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:Hematologic improvement
        Time Frame:9 months
        Safety Issue:No
        Description:Percent of subjects who have EITHER Hemoglobin improvement OR Platelet improvement as described above and no worsening of hemoglobin or platelets from baseline OR Percent of subjects who have Hemoglobin improvement as described above AND Did not develop platelets < 50 x 10e9/L Percent of subjects who have Platelet improvement as described above AND Did not develop Hemoglobin < 100 g/L or new transfusion dependence (Outcome parameter assessed is dependent on baseline hematology status)
        Measure:Symptom improvement
        Time Frame:9 months
        Safety Issue:No
        Description:Percent of subjects with 25% and 50% reduction in MPN-SAF Total Symptom Score from baseline at Week 36 Mean change from baseline in EORTC QLQ-C30 at 36 weeks Duration of all improvement parameters listed above
        Measure:Percent of subjects with complete response, partial response, clinical improvement, stable disease, and progressive disease according to IWG-MRT criteria
        Time Frame:9 months
        Safety Issue:No
        Description:

        Trial Keywords

        • fibrosis