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Trial record 1 of 1 for:    PRM-151 In Subjects With Primary Myelofibrosis
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A Phase 2 Study Of PRM-151 In Subjects With Myelofibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01981850
Recruitment Status : Active, not recruiting
First Posted : November 13, 2013
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Promedior, Inc.

Tracking Information
First Submitted Date  ICMJE October 29, 2013
First Posted Date  ICMJE November 13, 2013
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE October 1, 2013
Actual Primary Completion Date August 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2016)
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 ]
As determined by a central adjudication panel of expert hematopathologists, blinded to subject, treatment, and time of biopsy
Original Primary Outcome Measures  ICMJE
 (submitted: November 5, 2013)
Overall response rate according to International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2016)
  • Comparison of primary and secondary efficacy parameters between doses [ Time Frame: 9 months ]
  • Incidence of adverse events (AEs), serious adverse events (SAEs), and changes in laboratory test results [ Time Frame: up to 40 weeks ]
  • Bone marrow improvement: Bone marrow response rate at weeks 12, 24, and 36; Duration of bone marrow response [ Time Frame: 9 months ]
  • Hemoglobin improvement [ Time Frame: 9 months ]
    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)
  • Platelet improvement [ Time Frame: 9 months ]
    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)
  • Hematologic improvement [ Time Frame: 9 months ]
    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)
  • Symptom improvement [ Time Frame: 9 months ]
    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
  • Percent of subjects with complete response, partial response, clinical improvement, stable disease, and progressive disease according to IWG-MRT criteria [ Time Frame: 9 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2013)
  • Incidence of adverse events (AEs), serious adverse events (SAEs), and changes in laboratory test results [ Time Frame: up to 28 weeks ]
  • Change in bone marrow fibrosis according to European Consensus on Grading of Bone Marrow Fibrosis [ Time Frame: 6 months ]
  • Change in the modified Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) Score [ Time Frame: 6 months ]
  • Duration of response [ Time Frame: 6 months ]
  • Pharmacokinetic (PK) parameters including Cmax (maximum drug concentration), tmax (time to maximum concentration, area under the curve (AUC), clearance, and volume of distribution. [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures
 (submitted: January 15, 2016)
  • Exploratory Outcome: Bone marrow [ Time Frame: 9 months ]
    • Percent of subjects with Grade 0-1 bone marrow fibrosis grade at any time during the study and at weeks 12, 24, and 36
    • Duration of Grade 0-1 bone marrow fibrosis grade
    • Mean change from baseline to 12, 24, and 36 weeks in bone marrow fibrosis by quantitative image analysis
    • Changes from baseline to weeks 12, 24, and 36 in bone marrow metabolism by FDG or FLT PET scan (where feasible)
    • Assessment of changes in bone marrow morphology at 12, 24, and 36 weeks
  • Exploratory Outcome: Hematologic and other disease related laboratory parameters [ Time Frame: 9 months ]
    • Mean change from baseline to 36 weeks in: hemoglobin, # RBC units transfused in previous 12 weeks, platelet count, # platelet transfusions in previous 12 weeks, white blood cell count, absolute neutrophil count, reticulocyte count, peripheral blood blast count, and lactic dehydrogenase (LDH)
    • Percent of subjects with increase in Hgb from < 100 g/L to > 100 g/L without transfusions, increase in platelets from < 50 x 10e9/L to > 100 x 10e9/L, decrease in WBC from > 25 to < 25, increase in ANC from < 1500 to ≥ 1500, decrease in peripheral blood blasts from > 1% to < 1%, and disappearance of leukoerythroblastosis, at 36 weeks and for ≥ 12 weeks at any time during the study
    • Duration of increase in Hgb from < 100 g/L to > 100 g/L without transfusions, increase in platelets from < 50 x 10e9/L to > 100 x 10e9/L, decrease in WBC from > 25 to < 25, increase in ANC from < 1500 to ≥ 1500, decrease in peripheral blood blasts from > 1% to < 1%, and disappearance of leukoerythroblastosis
  • Exploratory Outcome: • Spleen improvement (subjects with palpable spleen at baseline) [ Time Frame: 9 months ]
    • Percent of subjects with 10% and 35% reduction in spleen size from baseline by CT at 36 weeks
    • Duration of 10% and 35% reduction in spleen size from baseline
    • Mean change from baseline in spleen size by CT at 36 weeks
    • Change in spleen and liver metabolism by FDG or FLT PET scan at 12, 24, and 36 weeks
  • Exploratory Outcome: DIPSS [ Time Frame: 9 months ]
    • Percent of subjects with a reduction in DIPSS score and category at week 36
    • Mean change in DIPSS score from baseline to Week 36
  • Exploratory Outcome: Mutational Status and Cytogentics [ Time Frame: 9 months ]
    • Association of baseline mutational status of JAK2V617F, MPLW515, Calreticulin, ASXL1, EZH2, SRSF2, IDH1/2 with selected primary and secondary endpoints
    • Changes in allele burden of JAK2V617F at week 36. Changes in allele burden of MPLW515, Calreticulin, ASXL1, EZH2, SRSF2, IDH1/2 at week 36 will be measured as commercially available assays become available
    • Association of baseline cytogenetic abnormalities and selected primary and secondary endpoints
  • Exploratory Outcome: Association of baseline PTX-2 levels with selected primary and secondary endpoints [ Time Frame: 9 months ]
  • Exploratory Outcome: • Evaluation of potential biomarkers of PRM-151 activity in bone marrow biopsies taken at baseline, weeks 12, 24, and 36 [ Time Frame: 9 months ]
  • Exploratory Outcome: Survival [ Time Frame: ongoing ]
    Measurement of progression-free and overall survival
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2 Study Of PRM-151 In Subjects With Myelofibrosis
Official Title  ICMJE 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)
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis
  • Polycythemia Vera
  • Post-Essential Thrombocythemia Myelofibrosis
Intervention  ICMJE Biological: PRM-151
IV infusion
Study Arms  ICMJE
  • Experimental: Cohort 1 0.3mg/kg Every 4 Weeks
    Subjects 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.
    Intervention: Biological: PRM-151
  • Experimental: Cohort 2 3 mg/kg Every 4 Weeks
    Subjects 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
    Intervention: Biological: PRM-151
  • Experimental: Cohort 3 10mg /kg Every 4 Weeks
    Subjects 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
    Intervention: Biological: PRM-151
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 7, 2016)
98
Original Estimated Enrollment  ICMJE
 (submitted: November 5, 2013)
104
Estimated Study Completion Date  ICMJE January 31, 2020
Actual Primary Completion Date August 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01981850
Other Study ID Numbers  ICMJE PRM-151G-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Promedior, Inc.
Study Sponsor  ICMJE Promedior, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bernt van den Blink, MD, PhD Promedior, Inc.
PRS Account Promedior, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP