Myeloid MalignancyPhase 1NCT07379125
Therapeutic RSK1 Targeting in Myeloid Malignancies
A Phase 1 study testing PMD-026 in people with Myeloid Malignancy, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This study hypothesizes that PMD-026, an oral inhibitor of ribosomal protein S6 kinase A1 (RSK1), is safe and well tolerated in participants with myelofibrosis (MF) and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPNs) and will improve spleen response, symptom response, and bone marrow… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloid Malignancy
- What is being tested?
- PMD-026
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2026to 31 Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of one of the following myeloid neoplasms determined by pathology review:
- Primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis in chronic phase according to the 2016 WHO criteria.
- Patients with MF must have had at least 1 prior JAK inhibitor treatment for a minimum of 12 weeks and their disease must have been determined to be resistant or refractory, and/or their response must have been lost or intolerant to treatment.
- MF must be Intermediate-2 or High-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS).
- Chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, juvenile myelomonocytic leukemia, or myelodysplastic / myeloproliferative neoplasm unclassifiable according to the 2016 WHO criteria
- 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 OR Baseline MFSAF v4.0 Total Symptom Score ≥ 10
Show all 18Show fewer
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Amy W Zhou, M.D., 314-362-8814, a.zhou@wustl.edu
Amy W Zhou, M.D.
About this study
This study hypothesizes that PMD-026, an oral inhibitor of ribosomal protein S6 kinase A1 (RSK1), is safe and well tolerated in participants with myelofibrosis (MF) and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPNs) and will improve spleen response, symptom response, and bone marrow histopathological response.
- Conditions
- Myeloid Malignancy
- Being tested
- PMD-026
- Keywords
- Myelofibrosis, Primary Myelofibrosis, Secondary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Splenomegaly, Anemia, Spleen volume, Spleen, Hematologic Diseases, Bone Marrow Diseases, Bone Marrow Cancer, Myeloproliferative Neoplasm, Chronic Myelomonocytic Leukemia, Atypical Chronic Myeloid Leukemia, Myelodysplastic Neoplasm with ring sideroblasts and thrombocytosis, Myeloproliferative Neoplasm with ring sideroblasts and thrombocytosis, Juvenile Myelomonocytic Leukemia
- Medical subject headings
- Primary Myelofibrosis, Splenomegaly, Anemia, Hematologic Diseases, Bone Marrow Diseases, Bone Marrow Neoplasms, Myeloproliferative Disorders, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PMD-026Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (MF patients): Dose Escalation Dose Level -1: PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
| Arm B (MDS/MPN patients): Dose Escalation Dose Level -1: PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
| Arm A (MF patients): Dose Escalation Dose Level 1 (Starting Dose): PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
| Arm B (MDS/MPN patients): Dose Escalation Dose Level 1 (Starting Dose): PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
| Arm A (MF patients): Dose Escalation Dose Level 2: PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
| Arm B (MDS/MPN patients): Dose Escalation Dose Level 2: PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
| Arm A (MF patients): Dose Expansion - Recommended Phase II Dose (RP2D): PMD-026 | Experimental | PMD-026 will be taken by mouth twice daily at the recommended phase II dose every day of each 28-day cycle. Receives: Drug: PMD-026 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
Graded per CTCAE v5.0.
Measured: From cycle 1 day 1 through 28 days after last dose (estimated to be 1 year and 28 days)
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.
Measured: During cycle 1 of treatment (each cycle is 28 days)
Recommended phase II dose (RP2D) (Dose Escalation only)
The RP2D will be determined based on review of safety and tolerability endpoints in dose escalation.
Measured: Completion of cycle 1 (each cycle is 28 days) of all dose-escalation patients (estimated to be 1 year and 28 days)
Changes in spleen size (Dose Expansion and RP2D Cohort in Dose Escalation)
Measured by ultrasound or other abdominal imaging.
Measured: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
Changes in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Total Symptom Score (Dose Expansion and PR2D Cohort in Dose Escalation)
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.
Measured: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
Bone marrow histopathologic response (Dose Expansion and RP2D Cohort in Dose Escalation)
Bone marrow histopathologic response will be evaluated by the disease specific criteria
Measured: Baseline and after 24 weeks of treatment (estimated to be 24 weeks)
Secondary outcomes (7)
Percentage of patients with 35% or greater reduction in spleen volume as determined by ultrasound or other imaging modalities
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
Percentage of participants with 25% or greater reduction in spleen volume as determined by ultrasound or other imaging modalities
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
Percentage of patients with a 50% or greater improvement in Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF) Total Symptom Score (TSS)
The MFSAF TSS 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.
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
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.
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
Overall response rate (ORR)
ORR is defined as the percentage of patients with CR, PR, or CI (if MF) + percentage of patients with CR, CR with resolution of symptoms, PR, MR, partial MR, or CB (if MDS/MPN).
Responses are defined by the International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria for participants with MF and by modified MDS/MPN International Working Group (MDS/MPN IWG) Response Criteria for participants with MDS/MPN.
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
Change in bone marrow fibrosis grading by WHO grading
The WHO scoring for bone marrow fibrosis is as follows: Grade 0 No fibrosis present, Grade 1 Mild fibrosis with some reticulin fibers present but not significantly affecting hematopoiesis, Grade 2 Moderate fibrosis where reticulin fibers are more prominent and begin to impact blood cell production, and Grade 3 Severe fibrosis characterized by extensive collagen deposition that severely impairs hematopoiesis.
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
Change in blast percentage in the bone marrow
Measured: At 24 weeks and at the end of treatment (estimated to be 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2026
- Study start20 May 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myeloid MalignancyStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Phoenix Molecular Designs, The Foundation for Barnes-Jewish Hospital, Swim Across America, Blood Cancer United
- Responsible party
- Sponsor
- Investigators
- Amy W Zhou, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07379125
- Sponsor's protocol ID
- 202603106
- Status last verified
- Oct 2026
- First submitted
- 23 Jan 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No