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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Promedior, Inc.
Sponsor:
Information provided by (Responsible Party):
Promedior, Inc.
ClinicalTrials.gov Identifier:
NCT01981850
First received: October 29, 2013
Last updated: January 8, 2014
Last verified: January 2014
  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.


Condition Intervention Phase
Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Biological: PRM-151
Drug: Ruxolitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, 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)

Resource links provided by NLM:


Further study details as provided by Promedior, Inc.:

Primary Outcome Measures:
  • Overall response rate according to International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events (AEs), serious adverse events (SAEs), and changes in laboratory test results [ Time Frame: up to 28 weeks ] [ Designated as safety issue: No ]
  • Change in bone marrow fibrosis according to European Consensus on Grading of Bone Marrow Fibrosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in the modified Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 104
Study Start Date: October 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Every 4 Weekly
subjects who have 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
Biological: PRM-151
recombinant human pentraxin-2
Other Name: recombinant human pentraxin-2
Experimental: Cohort 2 Weekly
subjects 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.
Biological: PRM-151
recombinant human pentraxin-2
Other Name: recombinant human pentraxin-2
Drug: Ruxolitinib
Other Name: Jakafi
Experimental: Cohort 2 Every 4 Weekly
subjects 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
Biological: PRM-151
recombinant human pentraxin-2
Other Name: recombinant human pentraxin-2
Drug: Ruxolitinib
Other Name: Jakafi
Experimental: Cohort 1 weekly
subjects who have 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
Biological: PRM-151
recombinant human pentraxin-2
Other Name: recombinant human pentraxin-2

Detailed Description:

This is 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 are two treatment cohorts, each assigned to one of two dose schedules of PRM-151. Subjects will be assigned to a weekly or every four week dosing schedule by the investigator based on their ability to visit the study site on a weekly basis. This is an adaptive design as defined in FDA Draft Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics, February 2010. Modifications to dose levels, schedule, or regimen may be made in Stage 2 based on data from Stage 1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (see Appendix C) or post ET/PV MF (note that all diagnoses must include the presence of at least Grade 2 marrow fibrosis according to the European Consensus on Grading of Bone Marrow Fibrosis (Appendix D) with intermediate -1, intermediate -2, or high risk disease according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Dynamic International Prognostic Scoring System (see Appendix E);

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

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

    6. Life expectancy of at least six months;

    7. At least two weeks must have elapsed between the last dose of any MF-directed drug treatments for myelofibrosis (including investigational therapies) and study enrollment, except for ruxolitinib for Cohort 2 (see Inclusion Criteria 11);

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

    9. 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 include use of oral contraceptives or Depo-Provera, with an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence.

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

    11. For Cohort 2 (PRM-151 added to ruxolitinib) Subjects only: Must have been on a stable dose of ruxolitinib treatment for at least 12 weeks with no further improvement in splenomegaly for at least four weeks;

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

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

    3. Presence of active serious infection;

    4. 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;

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

    6. Organ transplant recipients other than bone marrow transplant;

    7. Women who are pregnant or lactating.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01981850

Locations
United States, Arizona
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Ruben Mesa, MD    480-301-4961      
Contact: Vineta Ghurye    480-301-9191      
Principal Investigator: Ruben Mesa, MD         
United States, California
Stanford Cancer Institute Recruiting
Palo Alto, California, United States, 94304
Contact: Jason Gotlib, MD    650-725-0744      
Contact: Andrea Linder, MD    650-725-4047      
Principal Investigator: Jason Gotlib, MD         
United States, New York
Weil Cornell Medical Center Recruiting
New York, New York, United States, 10065
Contact: Ruth Bauman, RN    646-962-2700    rub9018@med.cornell.edu   
Contact: Ellen Ritchie, MD    646-962-2700    ritchie@med.cornell.edu   
Principal Investigator: Ellen Ritchie, MD         
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Sarah Han    212-241-9185    Sarah.han@mssm.edu   
Contact: Carrie Newsom, RN    212-241-9185    Carrie.newsom@mssm.edu   
Principal Investigator: John Mascarenhas, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Srdan Verstovsek, MD    713-745-3429      
Contact: Heather Schneider, RN    713-792-4478      
Principal Investigator: Srdan Verstovsek, MD         
Canada, British Columbia
Providence Health Care Recruiting
Vancouver, British Columbia, Canada, V6Z 2A5
Contact: Lynda Foltz, MD    604-684-5794      
Contact: Gail Viciente    604-682-2344      
Principal Investigator: Lynda Foltz, MD         
Canada, Ontario
The Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5T 2M9
Contact: Vikas Gupta, MD    416-946-4521      
Contact: Jayalakshm Ramanna    416-946-4501 ext 7808      
Principal Investigator: Vikas Gupta, MD         
Sponsors and Collaborators
Promedior, Inc.
Investigators
Study Director: Elizabeth G Trehu, MD Promedior, Inc.
  More Information

No publications provided

Responsible Party: Promedior, Inc.
ClinicalTrials.gov Identifier: NCT01981850     History of Changes
Other Study ID Numbers: PRM-151G-101
Study First Received: October 29, 2013
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Promedior, Inc.:
fibrosis

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on September 18, 2014