Therapeutic RSK1 Targeting in Myelofibrosis
ConditionMyelofibrosis
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
This is a phase Ib study evaluating PMD-026, an oral inhibitor of ribosomal protein S6 kinase A1 (RSK1), in participants with myelofibrosis (MF).The dose escalation portion utilizes a standard 3+3 design to evaluate two dose levels with an additional dose de-escalation portion to identify the recommended phase II dose (RP2D); subsequently, an additional 6 patients will be enrolled in the dose expansion portion evaluating the efficacy of PMD-026.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis in chronic phase, according to the 2016 WHO criteria
Patients must have had at least 1 prior JAK inhibitor treatment for a minimum of 12 weeks and their disease was determined resistant or refractory, and/or their response was lost or intolerant to treatment.
Intermediate-2 or High-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS).
Splenomegaly defined as estimated spleen volume of ≥450 cm3 by imaging with either MRI, CT or ultrasound, or a palpable spleen >=5 cm from the costal margin.
Disqualifiers
Prior allogeneic or autologous stem cell transplantation within the previous 12 months
Prior splenectomy
Prior splenic irradiation if < 3 months between last radiation and screening visit.
Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
Trial design
Design model
Sequential
Treatments tested in this trial
PMD-026
DrugPMD-026 is an oral drug which will be taken every 12 hours on an outpatient basis at the assigned dose every day of each 28-day cycle. Provided by Phoenix Molecular Designs.
Treatment groups
18 Participants
are divided into 4 treatment groupsGroup A: Dose Escalation Dose Level -1: PMD-026Experimental treatment 1 intervention
Group B: Dose Escalation Dose Level 1 (Starting Dose): PMD-026Experimental treatment 0 interventions
Group C: Dose Escalation Dose Level 2: PMD-026Experimental treatment 1 intervention
Group D: Dose Expansion - Recommended Phase II Dose (RP2D): PMD-026Experimental treatment 0 interventions
Trial outcomes
Primary outcomes
1
Number of participants with adverse events
Graded per CTCAE v5.0.
Time frame
From cycle 1 day 1 through 28 days after last dose (estimated to be 1 year and 28 days)2
Number of participants with dose limiting toxicities (DLTs) based on occurrence of serious treatment-emergent adverse events (Dose Escalation only)
Dose limiting toxicities are defined in the protocol.
Time frame
During cycle 1 of treatment (each cycle is 28 days)3
Recommended phase II dose (RP2D) (Dose Escalation only)
The RP2D will be determined based on review of safety and tolerability endpoints in dose escalation.
Time frame
Completion of cycle 1 (each cycle is 28 days) of all dose-escalation patients (estimated to be 1 year and 28 days)4
Changes in spleen size (Dose Expansion and RP2D Cohort in Dose Escalation)
Measured by ultrasound or other abdominal imaging.
Time frame
Baseline and after 24 weeks of treatment (estimated to be 24 weeks)Secondary outcomes
1
Percentage of patients with 35% or greater reduction in spleen volume as determined by ultrasound or other imaging modalities
Time frame
At 24 weeks and at the end of treatment (estimated to be 1 year)2
Percentage of participants with 25% or greater reduction in spleen volume as determined by ultrasound or other imaging modalities
Time frame
At 24 weeks and at the end of treatment (estimated to be 1 year)3
Percentage of patients with a 50% or greater improvement in Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) Total Symptom Score
The MFSAF assesses patient's symptom burden with 7-items that are scored from 0 (Absent) to 10 (Worst Imaginable). The total score can range from 0-70 with the higher score meaning more severe symptoms.
Time frame
At 24 weeks and at the end of treatment (estimated to be 1 year)4
Percentage of patients with a reduction in National Institutes of Health Patient Reported Outcomes Measurement Information System (NIH PROMIS) Short Form v2.0 - Physical Function 8c 7-day scores
The NIH PROMIS is a tool designed to assess physical function in adults. The tool at 8-items with scoring from 5 to 1. Total score is calculated by adding all scores together. The higher the score typically means better physical function.
Time frame
At 24 weeks and at the end of treatment (estimated to be 1 year)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
Phoenix Molecular Designs
Collaborator
The Foundation for Barnes-Jewish Hospital
Collaborator
Swim Across America
Collaborator
Source ClinicalTrials.gov