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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05308264
Recruitment Status : Recruiting
First Posted : April 4, 2022
Last Update Posted : October 10, 2023
Information provided by (Responsible Party):
Rigel Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Low Risk Myelodysplastic Syndromes Drug: R906289 Monosodium (R289 Na) Phase 1 Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 12, 2022
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Experimental
Dose Level 1: 250mg PO qd Dose Level 2: 500mg PO qd Dose Level 3: 750 mg PO qd and 1000 mg PO qd
Drug: R906289 Monosodium (R289 Na)
Drug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd,500 mg PO qd, 750 mg PO qd, 1000 mg PO qd)
Other Name: R906289 Monosodium

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. Participants with red blood cell transfusion independence by Week 24 [ Time Frame: 24 Weeks ]
    Proportion of participants who achieve ≥ 50% reduction in number of red blood transfusion compared to baseline and ≥ 24 weeks.

  2. Characterize pharmacokinetics (PK) [ Time Frame: 8 Weeks ]
    Maximum plasma concentration (Cmax)

Other Outcome Measures:
  1. Characterize pharmacodynamic (PD) [ Time Frame: 1 year ]
    Change from baseline biomarker expression levels in plasma and bone marrow (including but not limited to, C-reactive protein [CRP] and tumor necrosis factor [TNF]-a)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

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.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05308264

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Contact: Elizabeth Franklin (650) 624-1100
Contact: Donna Chow (650) 624-1100

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United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
University of California, Irvine Recruiting
Orange, California, United States, 92868
United States, Florida
Mount Sinai Medical Center Recruiting
Miami Beach, Florida, United States, 33140
University of Miami Recruiting
Miami, Florida, United States, 33136
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Rutgers Cancer Institute of New Jersey Withdrawn
New Brunswick, New Jersey, United States, 09083
United States, New York
Ichan School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
United States, Texas
University of Texas, Southwestern Recruiting
Dallas, Texas, United States, 75390
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Rigel Pharmaceuticals
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Responsible Party: Rigel Pharmaceuticals Identifier: NCT05308264    
Other Study ID Numbers: C-906289-002
First Posted: April 4, 2022    Key Record Dates
Last Update Posted: October 10, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rigel Pharmaceuticals:
Myelodysplastic Syndromes
Hematology Oncology
Hem/ Onc
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions