Recruitment

Recruitment Status
Completed
Estimated Enrollment
104

Inclusion Criterias

Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
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.
...
Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
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.
Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
Participants must voluntarily sign an ICF;
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;
Ability to adhere to the study visit schedule and all protocol requirements;
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 Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
Serum creatinine ≤ 2.5 mg/dL x ULN.
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);
A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score;
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;
Platelet count < 50 x 10e9/L, OR
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);

Exclusion Criterias

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

Summary

Conditions
  • Polycythemia Vera
  • Post-Essential Thrombocythemia Myelofibrosis
  • Primary Myelofibrosis
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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 rece...

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.

Inclusion Criterias

Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
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.
...
Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
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.
Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
Participants must voluntarily sign an ICF;
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;
Ability to adhere to the study visit schedule and all protocol requirements;
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 Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
Serum creatinine ≤ 2.5 mg/dL x ULN.
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);
A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score;
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;
Platelet count < 50 x 10e9/L, OR
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);

Exclusion Criterias

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

Locations

Atlanta, Georgia, 30322
Rotterdam, Zuid Holland, 3015 CE
London
Houston, Texas, 77030
Toronto, Ontario, M5T 2M9
...
Atlanta, Georgia, 30322
Rotterdam, Zuid Holland, 3015 CE
London
Houston, Texas, 77030
Toronto, Ontario, M5T 2M9
Paris, 75475
Kfar Saba, 4428164
Pesaro, 61122
Vancouver, British Columbia, V6Z 2A5
Palo Alto, California, 94304
Nijmegen, 6525 GA
Minden, 32429
Winston-Salem, North Carolina, 27157
Baltimore, Maryland, 21201
Pavia, 27100
Aachen, D-52074
New York, New York, 10065
Ann Arbor, Michigan, 48109-2800
New York, New York, 10029
Nashville, Tennessee, 37232
Boston, Massachusetts, 02215
Phoenix, Arizona, 85054
Jerusalem, 91120

Tracking Information

NCT #
NCT01981850
Collaborators
Not Provided
Investigators
Study Director: Clinical Trials Hoffmann-La Roche