Low Risk Myelodysplastic SyndromesPhase 1/2NCT05308264
Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)
A Phase 1/2 study testing R906289 Monosodium (R289 Na) in people with Low Risk Myelodysplastic Syndromes, run by Rigel Pharmaceuticals at 13 sites in United States.
Trial summary
Phase 1b Study of R289 in Patients with Lower-risk Myelodysplastic Syndromes (LR MDS) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low Risk Myelodysplastic Syndromes
- What is being tested?
- R906289 Monosodium (R289 Na)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 13 sitesUnited States
- Study dates
- 12 Sep 2022to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Patient must be ≥ 18 years of age at the time of signing the informed consent.
- Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
- Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.
- DOSE ESCALATION PHASE:
- Must meet at least one of the following criteria prior to initial administration of study treatment: 1) Symptomatic anemia with hemoglobin < 9.0 g/dL and no RBC transfusion within 16 of registration or 2) RBC transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin <9.0 g/dL.
- DOSE EXPANSION PHASE:
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- Relapsed, refractory to or ineligible for ESAs and has previously received one or more approved therapies for LR-MDS
- Must be RBC transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin <9.0 g/dL.
- EXPLORATORY PHASE 1b COHORT:
- Transfusion-dependent LR-MDS who are refractory or intolerant to, or are ineligible for ESAs.
- No prior therapy with any approved or investigational therapies for MDS
- No del 5q cytogenetic abnormality
- RBC transfusion dependent defined as receiving ≥ 2 units of PRBCs within 8 weeks in the preceding 16 weeks for a hemoglobin <9.0 g/dL
- All patients must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be >20% or a serum ferritin > 100ng/100mL
- Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.
- Must have adequate organ function, defined as:
- Hepatic function:
- aspartate amino transferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)
- total bilirubin ≤ 1.5 × ULN
- Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL
Who cannot join
- Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded < 4 weeks prior to study treatment
- Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
- MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
- Diagnosis of chronic myelomonocytic leukemia.
- History of uncontrolled seizures.
- Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).
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- History of other malignancy that could affect compliance or interpretation of results. Patients with an malignancy other than leukemia appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥ 2 years prior to study entry are eligible as are:
- Adequately treated in situ carcinoma of the cervix uteri
- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
- Low grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to the study, or previously resected.
- History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion (or following review by the Sponsor), could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
- Prior history of autologous or allogeneic stem cell transplantation
- Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds [msec]) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fridericia's QT correction formula.
- History of additional risk factors for TdP (e.g., symptomatic heart failure with left ventricular ejection fraction [LVEF] <40%, hypokalemia, family history of Long QT Syndrome).
- Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet. For any long-acting systemic agent such as a monoclonal antibody, study treatment should not begin within two half-lives of the agent.
- Use of concomitant medications that prolong the QT/QTc interval during study treatment
- Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 13 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
- Recruiting
University of Texas, Southwestern
Dallas, Texas, 75390
- Recruiting
Duke Cancer Institute
Durham, North Carolina, 27705
- Recruiting
Oncology Clinical Research Referral Office
Hackensack, New Jersey, 07601
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
- Recruiting
University of Miami
Miami, Florida, 33136
- Recruiting
Ichan School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
University of California, Irvine
Orange, California, 92868
- Recruiting
Stanford Cancer Institute
Palo Alto, California, 94304
- Recruiting
Intermountain Healthcare
Salt Lake City, Utah, 84009
- Recruiting
WashU Medicine
St Louis, Missouri, 63110
About this study
Official title: An Open-label, Phase 1b Study of R289, an IRAK1/4 Inhibitor, in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS) Who Are Relapsed/Refractory/Resistant to Prior Therapies
Phase 1b Study of R289 in Patients with Lower-risk Myelodysplastic Syndromes (LR MDS)
Read the detailed description
An open-label, Phase 1b study of R289, an IRAK 1/4 Inhibitor, to determine tolerability and preliminary efficacy in patients with LR MDS who are relapsed/refractory/resistant, intolerant, or have inadequate response to prior therapies such as erythropoietin (EPO), luspatercept, or hypomethylating agents (HMAs) for MDS.
- Conditions
- Low Risk Myelodysplastic Syndromes
- Being tested
- R906289 Monosodium (R289 Na)
- Keywords
- MDS, LR MDS, Myelodysplastic Syndromes, Hematology Oncology, Hem/ Onc
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R906289 Monosodium (R289 Na)Drug
Also called R906289 Monosodium
Drug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd, 250mg PO bid, 500 mg PO qd, 500 mg PO bid, 750 mg PO qd, split dose - 500 mg PO AM/250 mg PO PM)
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | ESCALATION PHASE:
Dose Level 1: 250mg PO qd Dose Level 2: 500mg PO qd Dose Level 3: 750 mg PO qd Dose Level 4: 250 mg PO bid Dose Level 5: 500 mg PO AM/250 mg PO PM Dose Level 6: 500 mg PO bid
EXPANSION PHASE (randomized 1:1):
Dose Level 1: 500 mg PO qd Dose Level 2: 500 mg PO bid Receives: Drug: R906289 Monosodium (R289 Na) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
- Incidence of adverse events (AEs)
- Incidence of discontinuation or interruptions of R289 due to AEs
- Incidence of dose limiting toxicities (DLTs)
Measured: 2 Year
Secondary outcomes (2)
Outcome Measure: Preliminary Efficacy
Measure Description Primary Efficacy:
Proportion of patients achieving red blood cell transfusions independence by ≥ 8 weeks, ≥ 16 weeks, and ≥ 24 weeks Proportion of patients with overall response per IWG 2006 Proportion of patients with hematologic improvement per IWG 2018 Time Frame: 24 Weeks Measure Description Characterized PK Maximum plasma concentration (Cmax) Time Frame: 8 Weeks
Measured: 24 Weeks for Primary Efficacy; 8 Weeks for Characterized PK
Characterize pharmacokinetics (PK)
Maximum plasma concentration (Cmax)
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2022
- Study start12 Sep 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low Risk Myelodysplastic SyndromesStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rigel Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05308264
- Sponsor's protocol ID
- C-906289-002
- Status last verified
- Nov 2026
- First submitted
- 2 Mar 2022
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 1b Study of R289, an IRAK1/4 Inhibitor, in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS) Who Are Relapsed/Refractory/Resistant to Prior Therapies
- ClinicalTrials.gov ID
- NCT05308264
- Acronym / sponsor ID
- C-906289-002
- Conditions
- Low Risk Myelodysplastic Syndromes
- Keywords
- MDS, LR MDS, Myelodysplastic Syndromes, Hematology Oncology, Hem/ Onc
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- Rigel PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Sep 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 4 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1b Study of R289 in Patients with Lower-risk Myelodysplastic Syndromes (LR MDS)
Detailed description
An open-label, Phase 1b study of R289, an IRAK 1/4 Inhibitor, to determine tolerability and preliminary efficacy in patients with LR MDS who are relapsed/refractory/resistant, intolerant, or have inadequate response to prior therapies such as erythropoietin (EPO), luspatercept, or hypomethylating agents (HMAs) for MDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: R906289 Monosodium (R289 Na)ESCALATION PHASE: Dose Level 1: 250mg PO qd Dose Level 2: 500mg PO qd Dose Level 3: 750 mg PO qd Dose Level 4: 250 mg PO bid Dose Level 5: 500 mg PO AM/250 mg PO PM Dose Level 6: 500 mg PO bid EXPANSION PHASE (randomized 1:1): Dose Level 1: 500 mg PO qd Dose Level 2: 500 mg PO bid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patient must be ≥ 18 years of age at the time of signing the informed consent.
- Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
- Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.
- DOSE ESCALATION PHASE:
- DOSE EXPANSION PHASE:
Key exclusion criteria (17 listed)
- Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded < 4 weeks prior to study treatment
- Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
- MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
- Diagnosis of chronic myelomonocytic leukemia.
- History of uncontrolled seizures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| R906289 Monosodium (R289 Na)Also: R906289 MonosodiumDrug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd, 250mg PO bid, 500 mg PO qd, 500 mg PO bid, 750 mg PO qd, split dose - 500 mg PO AM/250 mg PO PM) | Drug | Experimental |
Primary outcome
Safety and Tolerability
Time frame: 2 Year
* Incidence of adverse events (AEs) * Incidence of discontinuation or interruptions of R289 due to AEs * Incidence of dose limiting toxicities (DLTs)
2 secondary outcomes
Outcome Measure: Preliminary Efficacy
Time frame: 24 Weeks for Primary Efficacy; 8 Weeks for Characterized PK
Characterize pharmacokinetics (PK)
Time frame: 8 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing R906289 Monosodium (R289 Na) in people with Low Risk Myelodysplastic Syndromes, run by Rigel Pharmaceuticals at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Strait Hicklin ((650) 624-1100, shicklin@rigel.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: 2 Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.