R289 for Myelodysplastic Syndrome

Recruiting at 14 trial locations

Overseen By Strait Hicklin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Rigel Pharmaceuticals

Must not be taking: QT prolonging, CYP3A inhibitors

Disqualifiers: Chronic myelomonocytic leukemia, Uncontrolled infections, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

86 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called R289 (R906289 Monosodium) for individuals with lower-risk myelodysplastic syndromes (LR MDS). The aim is to evaluate the safety and effectiveness of R289 in various doses for those who have not responded well to standard treatments. Suitable candidates for this trial include those who frequently require red blood cell transfusions and have unsuccessfully tried other MDS treatments. As a Phase 1, Phase 2 trial, participants will be among the first to help researchers understand how R289 works and assess its effectiveness in an initial group.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that prolong the QT/QTc interval or are strong CYP3A or CYP2B6 inhibitors or inducers during the study. If you are on any of these medications, you may need to stop them before participating.

Is there any evidence suggesting that R906289 Monosodium (R289 Na) is likely to be safe for humans?

Research shows that R289, the treatment under study, has been generally well tolerated by patients. Early results indicate that older patients with less severe myelodysplastic syndromes, who have undergone many prior treatments, responded well to R289. Reports revealed no major safety concerns, as most patients did not experience serious side effects. The ongoing study aims to determine the optimal dose for future research. Overall, current data suggests the treatment appears safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for myelodysplastic syndrome, which often include chemotherapy or supportive care like blood transfusions and growth factors, R906289 Monosodium (R289 Na) is unique because it offers a novel approach through its distinct dosing strategies. This investigational drug has multiple dosing levels, providing flexibility to find the most effective and tolerable regimen for patients. Researchers are excited about R289 Na because it has the potential to directly target the underlying issues of the disease with possibly fewer side effects, which could improve patient outcomes significantly.

What evidence suggests that R289 might be an effective treatment for Myelodysplastic Syndrome?

Research has shown that R289, which participants in this trial will receive, is being tested for its potential to help people with lower-risk myelodysplastic syndromes (LR MDS). R289 blocks certain proteins, called IRAK 1/4, that can promote cancer cell growth. Early results suggest that R289 is generally safe for patients who have tried other treatments, as most did not experience serious side effects. On average, patients remained on the treatment for about 4.6 months, indicating potential benefits for those with LR MDS. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My MDS hasn't responded well to standard treatments like TPOs, EPOs, or HMAs.

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

My liver and kidney functions are within normal ranges.

Exclusion Criteria

I have had a bone marrow transplant in the past.

I haven't had cancer in the last 2 years, except for certain skin cancers or cervical cancer.

I have risk factors for a specific heart rhythm problem, including weak heart function or low potassium.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive R289 at varying doses to determine tolerability and preliminary efficacy

24 weeks

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term safety and pharmacodynamic changes

1 year

What Are the Treatments Tested in This Trial?

Interventions

• R906289 Monosodium (R289 Na)

Trial Overview 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.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

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

R906289 Monosodium (R289 Na) is already approved in United States for the following indications:

Approved in United States as R289 for:

• Lower-risk Myelodysplastic Syndromes (LR MDS)

Who Is Running the Clinical Trial?

Rigel Pharmaceuticals

Lead Sponsor

Trials

37

Recruited

4,000+

Citations

1. rigel.com rigel.com/investors/news-events/press-releases/detail/404/rigel-highlights-initial-data-from-ongoing-phase-1b-study

Rigel Highlights Initial Data from Ongoing Phase 1b Study ... The median time on therapy was 4.6 months (range: 0.9-22.4 months). R289 was generally well-tolerated in this heavily pretreated LR-MDS patient ...

2. trial.medpath.com trial.medpath.com/clinical-trial/d09fe03585555a3a/nct05308264-open-label-1b-r289-irak1-4-inhibitor-participants-lower-risk

Study of R289 in Patients With Lower-risk Myelodysplastic ... An open-label, Phase 1b study of R289, an IRAK 1/4 Inhibitor, to determine tolerability and preliminary efficacy in patients with LR MDS who are ...

3. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper206096.html

Paper: R289, a Dual Irak 1/4 Inhibitor, in ... Conclusions: At data cutoff, R289 was well-tolerated in this heavily pretreated LR-MDS patient population, the majority of whom were HTB. The ...

4. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0186.html

An Open-label, Phase 1b Study of R289, an IRAK1/4 ... An open-label, Phase 1b study of R289, an IRAK1/4 inhibitor, in patients with lower-risk myelodysplastic syndromes (LR MDS) who are relapsed/refractory/ ...

5. clinicaltrials.icts.uci.edu clinicaltrials.icts.uci.edu/trial/NCT05308264

Study of R289 in Patients With Lower-risk Myelodysplastic ... An open-label, Phase 1b study of R289, an IRAK 1/4 Inhibitor, to determine tolerability and preliminary efficacy in patients with LR MDS who ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/338645

Study of R289 in Patients With Lower-risk Myelodysplastic ... Secondary outcome measures ; Outcome measure. Characterize pharmacokinetics (PK) ; Measure description. Maximum plasma concentration (Cmax) ; Time frame. 8 Weeks ...

7. rigel.com rigel.com/investors/news-events/press-releases/detail/420/rigel-announces-first-patient-enrolled-in-the-dose

Press Releases Dose expansion phase will determine the recommended Phase 2 dose of R289 for patients with transfusion dependent R/R lower-risk MDS.