What side effects are associated with this type of intervention?

Common treatments for Myelodysplastic Syndrome (MDS) include hypomethylating agents such as azacitidine and decitabine. These treatments are associated with several side effects, including cytopenias (low blood cell counts), febrile neutropenia (fever with low white blood cell count), and an increased risk of infections. Patients often require hospitalization for neutropenic fever. Other side effects may include liver and kidney function abnormalities, necessitating regular monitoring and potential dose adjustments. Growth factor support may be needed to manage some of these side effects.

What prior FDA approvals exist?

The FDA has approved hypomethylating agents such as azacitidine and decitabine for the treatment of Myelodysplastic Syndrome (MDS). These agents are effective in managing the disease by modifying the DNA methylation process. Additionally, thrombopoietin mimetics like romiplostim and eltrombopag have been evaluated for their potential to improve platelet counts in MDS patients, although their use is controversial due to concerns about increasing the risk of progression to acute myeloid leukemia (AML).

What other types of research exist?

Promising novel alternatives for Myelodysplastic Syndrome (MDS) patients include hypomethylating agents (HMAs) like azacitidine and decitabine, especially when combined with venetoclax. Venetoclax, a BCL2 inhibitor, has shown improved outcomes when used with HMAs in AML and may offer similar benefits in MDS. Additionally, MDM2 antagonists like idasanutlin are under investigation and may provide new therapeutic options. These treatments are supported by clinical trials demonstrating their efficacy and safety profiles.

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R289 for Myelodysplastic Syndrome

Phase 1 & 2

Recruiting

Research Sponsored by Rigel Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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 have adequate organ function, defined as: Hepatic function: 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

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called R289 to see if it is safe and effective for patients with lower-risk myelodysplastic syndromes who haven't responded to other treatments.

Who is the study for?

This trial is for adults over 18 with lower-risk Myelodysplastic Syndromes (LR MDS) who haven't responded well to other treatments like TPOs, EPOs, luspatercept, and HMAs. They should have low bone marrow myeloblasts and issues like needing blood transfusions or having low platelet counts. Participants need good liver and kidney function and can't join if they've had recent MDS treatment or certain health problems.

What is being tested?

The study tests R289 Na in patients with LR MDS to see its safety and effectiveness. It's a Phase 1b trial which means it's early in the testing process focusing on how people react to the drug at different doses.

What are the potential side effects?

While specific side effects of R289 Na aren't listed here, similar drugs may cause fatigue, nausea, blood count changes, or organ inflammation. Side effects depend on individual reactions to the medication.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My MDS is classified as very low, low, or intermediate-1 risk with ≤5% bone marrow blasts.

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My liver and kidney functions are within normal ranges.

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I am 18 years old or older.

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I need regular blood transfusions or have had a low platelet count in the last 8 weeks.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a bone marrow transplant in the past.

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My heart's electrical cycle is longer than normal.

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I do not have an uncontrolled infection like HIV or hepatitis.

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I have been diagnosed with chronic myelomonocytic leukemia.

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I have a history of seizures that are not controlled by medication.

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My MDS was caused by previous cancer or autoimmune disease treatment.

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I am not taking strong medication that affects liver enzymes during the study.

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I am not taking any medications that affect my heart's rhythm.

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I have severe anemia due to a deficiency or bleeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety and Tolerability

Secondary study objectives

Characterize pharmacokinetics (PK)

Participants with red blood cell transfusion independence by Week 24

Other study objectives

Characterize pharmacodynamic (PD)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: ExperimentalExperimental Treatment1 Intervention

Dose Level 1: 250mg PO qd Dose Level 2: 500mg PO qd Dose Level 3: 750 mg PO qd and 1000 mg PO qd

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Myelodysplastic Syndrome (MDS) include erythropoiesis-stimulating agents (ESAs), thrombopoietin mimetics, and DNA methyltransferase inhibitors. ESAs work by stimulating the bone marrow to produce more red blood cells, which can alleviate anemia and reduce the need for transfusions. Thrombopoietin mimetics, such as romiplostim, aim to increase platelet production, though their use is controversial due to potential risks of leukemic transformation. DNA methyltransferase inhibitors, like azacitidine and decitabine, work by reversing abnormal DNA methylation patterns, thereby restoring normal function to genes that control cell growth and differentiation. These treatments are crucial for managing the hematologic complications of MDS, improving patients' quality of life, and potentially altering the disease course.

Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.Combination therapy with DNA methyltransferase inhibitors in hematologic malignancies.