NCT07379125 · Washington University School of Medicine
Therapeutic RSK1 Targeting in Myelofibrosis
What this study is about
This is a phase Ib study evaluating PMD-026, an taken by mouth inhibitor of ribosomal protein S6 kinase A1 (RSK1), in participants with myelofibrosis (MF).
View original scientific description
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.
Interventions
DRUG
PMD-026
PMD-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.
Primary outcome measures
Number of participants with adverse events
Time frame: From cycle 1 day 1 through 28 days after last dose (estimated to be 1 year and 28 days)
Graded per CTCAE v5.0.
Number of participants with dose limiting toxicities (DLTs) based on occurrence of serious treatment-emergent adverse events (Dose Escalation only)
Time frame: During cycle 1 of treatment (each cycle is 28 days)
Dose limiting toxicities are defined in the protocol.
Recommended phase II dose (RP2D) (Dose Escalation only)
Time frame: Completion of cycle 1 (each cycle is 28 days) of all dose-escalation patients (estimated to be 1 year and 28 days)
The RP2D will be determined based on review of safety and tolerability endpoints in dose escalation.
Changes in spleen size (Dose Expansion and RP2D Cohort in Dose Escalation)
Time frame: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
Measured by ultrasound or other abdominal imaging.
Changes in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Total Symptom Score (Dose Expansion and PR2D Cohort in Dose Escalation)
Time frame: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
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.
Bone marrow histopathologic response (Dose Expansion and RP2D Cohort in Dose Escalation)
Time frame: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
Bone marrow histopathologic response will be evaluated by the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.
Overall response rate (ORR) (Dose Expansion and RP2D Cohort in Dose Escalation)
Time frame: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
Defined as CR (complete remission/response) + PR (partial remission/response) + CI (clinical improvement). Responses are defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) consensus.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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).
- Presence of measurable disease as defined by:
- 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.
- Baseline MFSAF v4.0 Total Symptom Score ≥ 10
- At least 18 years of age.
- ECOG performance status ≤ 2.
- Adequate organ function as defined below:
- Total bilirubin ≤ 1.5 x IULN (unless the participant has a history of Gilbert's syndrome)
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
- Adequate laboratory parameters:
- Absolute Neutrophil Count (ANC) ≥ 100/mm\^3
- Platelets ≥50,000/mm\^3
- Blasts ≤ 10% on manual differential
- The effects of PMD-026 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion criteria
- 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.
- Currently receiving any other investigational agents or planning to receive any investigational agents within 28 days before the planned first dose of PMD-026.
- Currently receiving a JAK inhibitor or planning to receive a JAK inhibitor within 7 days before the planned first dose of PMD-026. In patients with ongoing JAK inhibitor therapy (i.e. ruxolitinib) at screening, it must be tapered over a period of at least 7 days. Patients on a low dose of ruxolitinib (e.g. 5 mg QD) may have a reduced taper period or no taper.
- Known active disease involving the CNS.
- QTcF \>450 msec for males, \>470 msec for females (calculated using Fridericia's formula).
- A history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to PMD-026 or other agents used in the study.
- Any major surgery within 28 days prior to the first dose of PMD-026.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Unable to swallow or retain oral medications.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 35 days of study entry (repeated on C1D1).
Where
- St Louis, Missouri
Collaborators
Phoenix Molecular Designs, The Foundation for Barnes-Jewish Hospital, Swim Across America
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 22, 2026 · Source of record for eligibility and locations