Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)

Rigel Pharmaceuticals (Industry)
Overall Status
Not yet recruiting ID

Study Details

Study Description

Brief Summary

The study will be an open-label, Phase 1b study of R289 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), thrombopoietin (TPO), luspatercept, or hypomethylating agents (HMAs) for MDS.

Condition or Disease Intervention/Treatment Phase
  • Drug: R906289 Monosodium (R289 Na)
Phase 1/Phase 2

Study Design

Study Type:
Anticipated Enrollment :
22 participants
Intervention Model:
Single Group Assignment
None (Open Label)
Primary Purpose:
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 Refractory/Resistant to Prior Therapies
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Apr 1, 2024
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation

Experimental: Dose Expansion Phase

Drug: R906289 Monosodium (R289 Na)
250 mg tablet

Outcome Measures

Primary Outcome Measures

  1. Safety and Tolerability [2 Year]

    Incidence of adverse events (AEs) Incidence of discontinuation or interruptions of R289 due to AEs Incidence of dose limiting toxicities (DLTs)

Eligibility Criteria


Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:
  • 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 TPOs, EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.

  • Must meet at least one of the disease-related criteria for RBC transfusion, platelet count, or absolute neutrophil (ANC) within 8 weeks prior to initial administration of study treatment:

  1. Symptomatic anemia untransfused with hemoglobin < 9.0 g/dL within 8 weeks of registration or red blood cell (RBC) transfusion dependent defined as receiving > 3 units of packed red blood cells (PRBCs) in the preceding 16 weeks for a hemoglobin <9.0 g/dL.

  2. Clinically relevant thrombocytopenia (platelet counts of <100 × 109/L in at least 2 blood counts prior to study treatment and transfusion dependence).

  3. Absolute neutrophil count (ANC) of < 1.0 × 109/L in at least 2 blood counts prior to randomization.

  • Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.

  • Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.

  • Must have adequate organ function, defined as:

  1. Hepatic function:
  • aspartate amino transferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)

  • total bilirubin ≤ 1.5 × ULN

  1. Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL
Exclusion Criteria:
  • 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.

  • All subjects must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/100 mL.

  • 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).

  • History of an active malignancy within the past 2 years prior to study entry, with the exception of:

  1. Adequately treated in situ carcinoma of the cervix uteri

  2. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or

  3. Any other malignancy with a life expectancy of more than 2 years

  • 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, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.

  • Prior history of bone marrow 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., heart failure, hypokalemia, family history of Long QT Syndrome).

  • Treatment with cytotoxic chemotherapeutic agents or experimental agents for the treatment of MDS within 8 weeks of study treatment.

  • Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 8 weeks of initiating study treatment).

  • 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

Contacts and Locations


No locations specified.

Sponsors and Collaborators

  • Rigel Pharmaceuticals


None specified.

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
Rigel Pharmaceuticals Identifier:
Other Study ID Numbers:
  • C-906289-002
First Posted:
Apr 4, 2022
Last Update Posted:
Jul 27, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Keywords provided by Rigel Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 27, 2022