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

NCT05308264 | Recruiting Phase 1 FDA Drug

• 1 other identifier: C-906289-002
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 15

Brief Summary

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

Conditions

Low Risk Myelodysplastic Syndromes

Keywords

MDS; LR MDS; Myelodysplastic Syndromes; Hematology Oncology; Hem/ Onc

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

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

  2 Year

Secondary Outcomes (2)

• Outcome Measure: Preliminary Efficacy

  24 Weeks for Primary Efficacy; 8 Weeks for Characterized PK

• Characterize pharmacokinetics (PK)

  8 Weeks

Other Outcomes (1)

• Characterize pharmacodynamic (PD)

  1 year

Study Arms (1)

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: 250 mg PO qd Dose Level 2: 250 mg PO bid

Drug: R906289 Monosodium (R289 Na)

Interventions

R906289 Monosodium (R289 Na) DRUG

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)

Also known as: R906289 Monosodium

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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:
• 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.

You may not qualify 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 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.

Sponsors & Collaborators

• Rigel Pharmaceuticals: lead

Study Sites (15)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California, Irvine

Orange, California, 92868, United States

RECRUITING

Stanford Cancer Institute

Palo Alto, California, 94304, United States

NOT YET RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

WITHDRAWN

WashU Medicine

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

Oncology Clinical Research Referral Office

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 09083, United States

WITHDRAWN

Ichan School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27705, United States

NOT YET RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

NOT YET RECRUITING

University of Texas, Southwestern

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Intermountain Healthcare

Salt Lake City, Utah, 84009, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Strait Hicklin

CONTACT

(650) 624-1100; shicklin@rigel.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: April 4, 2022
• Study Start: September 12, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)