Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)
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|ClinicalTrials.gov Identifier: NCT05308264|
Recruitment Status : Recruiting
First Posted : April 4, 2022
Last Update Posted : March 15, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Low Risk Myelodysplastic Syndromes||Drug: R906289 Monosodium (R289 Na)||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 12, 2022|
|Estimated Primary Completion Date :||April 2024|
|Estimated Study Completion Date :||May 2024|
Dose Level 1: 250mg PO qd Dose Level 2: 500mg PO qd
Drug: R906289 Monosodium (R289 Na)
Drug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd or 500 mg PO qd)
Other Name: R906289 Monosodium
- 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)
- Subjects with red blood cell transfusion independence by Week 24 [ Time Frame: 24 Weeks ]Proportion of subjects who achieve ≥ 50% reduction in number of red blood transfusion compared to baseline and ≥ 24 weeks.
- Characterize pharmacokinetics (PK) [ Time Frame: 8 Weeks ]Maximum plasma concentration (Cmax)
- 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)
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.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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, or platelet count within 8 weeks prior to initial administration of study treatment:
- 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.
- Clinically relevant thrombocytopenia (platelet counts of <100 × 109/L in at least 2 blood counts prior to study treatment and transfusion dependence).
All subjects must have documented marrow iron stain. 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:
- aspartate amino transferase (AST) or 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
- 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:
- Adequately treated in situ carcinoma of the cervix uteri
- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
- 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).
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT05308264
|Contact: Elizabeth Franklin||(650) email@example.com|
|Contact: Donna Chow||(650) firstname.lastname@example.org|
|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||Recruiting|
|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, Texas|
|University of Texas, Southwestern||Recruiting|
|Dallas, Texas, United States, 75390|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Responsible Party:||Rigel Pharmaceuticals|
|Other Study ID Numbers:||
|First Posted:||April 4, 2022 Key Record Dates|
|Last Update Posted:||March 15, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Bone Marrow Diseases