Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Orange, California and other locations
Dates
study started
completion around

Description

Summary

Phase 1b Study of R289 in Participants with Lower-risk Myelodysplastic Syndromes (LR MDS)

Official Title

An Open-label, Phase 1b Study of R289, an IRAK1/4 Inhibitor, in Participants With Lower-risk Myelodysplastic Syndromes (LR MDS) Who Are Refractory/Resistant to Prior Therapies

Details

An open-label, Phase 1b study of R289 to determine tolerability and preliminary efficacy in participants 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.

Keywords

Low Risk Myelodysplastic Syndromes, MDS, LR MDS, Myelodysplastic Syndromes, Hematology Oncology, Hem/ Onc, Preleukemia, Syndrome, R906289 Monosodium (R289 Na)

Eligibility

You can join if…

Open to people ages 18 years and up

  • Participant 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). Participants with del (5q) must have failed prior lenalidomide therapy.
  • Must be blood transfusion dependent and meet at least one of the disease-related criteria for RBC transfusion, or platelet count 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 ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks 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).

      All participants 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:
    1. Hepatic function:
      • aspartate amino transferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)
      • total bilirubin ≤ 1.5 × ULN
    2. Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL

You CAN'T join if...

  • 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).
  • 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., 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.
  • 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

Locations

  • University of California, Irvine accepting new patients
    Orange California 92868 United States
  • University of California, Los Angeles accepting new patients
    Los Angeles California 90095 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Rigel Pharmaceuticals
ID
NCT05308264
Phase
Phase 1/2 Myelodysplastic Syndrome Research Study
Study Type
Interventional
Participants
Expecting 34 study participants
Last Updated