Imetelstat for Myelodysplastic Syndrome

Not currently recruiting at 187 trial locations

Overseen By Souria Dougherty

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Geron Corporation

Must not be taking: Corticosteroids, Chemotherapy, Immunosuppressive, others

Disqualifiers: Heart disease, Hypertension, Arrhythmia, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment, imetelstat sodium, for individuals with myelodysplastic syndrome (MDS) who require regular blood transfusions and have not responded to standard ESA treatments. The study aims to determine if this medication can reduce or eliminate the need for red blood cell transfusions. Participants should have low or intermediate-1 risk MDS and require frequent blood transfusions. Some parts of the trial will compare imetelstat (also known as Rytelo or GRN163L) to a placebo, while another part examines its effect on heart rhythms. The goal is to find a safe and effective treatment to improve daily life for those with MDS. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. You must not have taken corticosteroids over 30 mg/day, growth factors, erythropoiesis-stimulating agents, or certain other therapies within 4 weeks before starting the study (8 weeks for long-acting ESAs).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that imetelstat is generally safe for treating lower-risk myelodysplastic syndrome (MDS). Studies indicate that patients might experience a temporary drop in blood cells, known as transient cytopenias, but this is usually manageable. Some patients have also reported reduced fatigue. Although detailed long-term safety information is not yet available, the treatment has shown promise in reducing the need for blood transfusions. More research is needed to fully understand its long-term effects, but current data suggests it is well-tolerated by many patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for myelodysplastic syndrome?

Researchers are excited about imetelstat for treating myelodysplastic syndrome because it offers a novel approach by targeting telomerase, an enzyme crucial for the survival of cancer cells. Unlike traditional treatments like hypomethylating agents (HMAs) or lenalidomide, which modify the cancer cell environment, imetelstat directly inhibits telomerase activity, potentially leading to cancer cell death. This unique mechanism could offer hope for patients who do not respond well to current therapies, providing a more targeted attack on the disease.

What evidence suggests that imetelstat might be an effective treatment for myelodysplastic syndrome?

Research has shown that imetelstat, which participants in this trial may receive, may help treat myelodysplastic syndrome (MDS), particularly for patients requiring regular blood transfusions. In one study, 40% of patients who received imetelstat went at least 8 weeks without needing a transfusion, compared to only 15% in a group that did not receive the drug. Patients also experienced an average increase in hemoglobin levels by 3.6 grams per deciliter, reducing problems related to anemia. Imetelstat appears to improve the overall production of blood cells, potentially reducing other health issues related to MDS. These findings suggest that imetelstat could be a viable option for those whose condition hasn't improved with other treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Tymara Berry, MD

Principal Investigator

Geron Corporation

Are You a Good Fit for This Trial?

Adults over 18 with low or intermediate-1 risk Myelodysplastic Syndrome (MDS) who need regular blood transfusions and haven't responded to standard treatments can join. They must have an ECOG performance status of 0, 1, or 2, indicating they are fully active or have some limitations but don't require full-time care.

Inclusion Criteria

I have been diagnosed with MDS or MDS/MPN-RS-T by a bone marrow test in the last 12 weeks.

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

My MDS is classified as low or intermediate-1 risk.

Exclusion Criteria

I haven't taken high-dose steroids or growth factors in the last 4 weeks.

I haven't taken any cancer or immune system treatments in the last 4 weeks.

I have a long-term irregular heartbeat.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment Phase 2

Participants receive imetelstat sodium in an open-label, single-arm design

Up to 5 years

Every 4 weeks (on a 28-day cycle)

Treatment Phase 3

Participants receive imetelstat sodium or placebo in a double-blind, randomized design

Up to 3.7 years

Every 4 weeks (on a 28-day cycle)

Ventricular Repolarization Substudy

Evaluate the effect of imetelstat sodium on ventricular repolarization

Minimum of 2 treatment cycles

Every 4 weeks (on a 28-day cycle)

Extension Phase

Continued treatment for participants benefiting from imetelstat sodium and evaluation of long-term safety and overall survival

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Imetelstat
• Placebo

Trial Overview The trial is testing Imetelstat's effectiveness in improving the condition of MDS patients who rely on blood transfusions after not responding to other treatments. Part of the group will receive Imetelstat while another part will get a placebo for comparison.

How Is the Trial Designed?

Group I: QTc Substudy: Imetelstat Sodium Experimental Treatment 1 Intervention

Imetelstat sodium administered IV, at a starting dose of 7.5 mg/kg, every 4 weeks (on a 28-day cycle) until death, lost to follow-up, withdrawal of consent, or study termination whichever occurs first.

Group II: Phase 3: Imetelstat Sodium Experimental Treatment 1 Intervention

Imetelstat sodium administered IV, at a starting dose of 7.5 mg/kg, every 4 weeks (on a 28-day cycle) until death, lost to follow-up, withdrawal of consent, or study termination whichever occurs first.

Group III: Phase 2: Imetelstat Sodium Experimental Treatment 1 Intervention

Imetelstat sodium administered intravenously (IV), at a starting dose of 7.5 milligrams per kilogram (mg/kg), every 4 weeks (on a 28-day cycle) until death, lost to follow-up, withdrawal of consent, or study termination whichever occurs first. Dose escalation to 9.4 mg/kg was allowed before Protocol Amendment 2.

Group IV: Extension Phase: Imetelstat Sodium Experimental Treatment 1 Intervention

Participants randomized to the imetelstat sodium arm in the Phase 3 and the VR QTc Substudy, based on the response will continue to receive imetelstat sodium IV, at the dose they were receiving in the Phase 3 or VR QTc Substudy, every 4 weeks (on a 28-day cycle) until death, lost to follow-up, withdrawal of consent, study termination, or up to 3 years whichever occurs first.

Group V: Extension Phase: Extended Follow-up Experimental Treatment 1 Intervention

Participants randomized to the placebo arm in the Phase 3 study will enter the Extended Follow-up part of the Extension Phase and continue in follow up until death, lost to follow-up, withdrawal of consent, study termination, or whichever occurs first up to approximately 3 years.

Group VI: Phase 3: Placebo Placebo Group 1 Intervention

Imetelstat sodium-matching placebo administered IV, every 4 weeks (on a 28-day cycle), until death, lost to follow-up, withdrawal of consent, or study termination whichever occurs first.

Group VII: QTc Substudy: Placebo Placebo Group 1 Intervention

Imetelstat sodium-matching placebo administered IV, every 4 weeks (on a 28-day cycle), until death, lost to follow-up, withdrawal of consent, or study termination whichever occurs first. If after a minimum of 2 treatment cycles a participant has no significant change to pRBC transfusion burden or evidence of clinical benefit per Investigator, after discussion with the Sponsor the participant, he/she may be permitted to start treatment with imetelstat sodium.

Imetelstat is already approved in United States for the following indications:

Approved in United States as Rytelo for:

• Transfusion-dependent low- to intermediate-risk myelodysplastic syndromes

Who Is Running the Clinical Trial?

Geron Corporation

Lead Sponsor

Trials

20

Recruited

1,500+

Published Research Related to This Trial

There have been no new drug approvals for myelodysplastic syndromes (MDS) in 13 years, highlighting a significant gap in treatment advancements since decitabine was approved in 2006.

Emerging therapies like luspatercept and imetelstat show promise for treating symptomatic anemia in lower-risk MDS patients, and future treatments are expected to be more personalized based on genetic and biomarker analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving therapies for lower-risk myelodysplastic syndromes. Bewersdorf, JP., Zeidan, AM.[2020]

Imetelstat showed promising efficacy in treating high-risk or intermediate-2-risk myelofibrosis, with 21% of patients achieving complete or partial remission, and a median duration of response of 18 months for complete responses.

However, the treatment was associated with significant adverse effects, including severe thrombocytopenia in 18% of patients and neutropenia in 12%, indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. Tefferi, A., Lasho, TL., Begna, KH., et al.[2022]

Luspatercept-aamt, approved by the FDA in April 2020, effectively promotes erythroid maturation and demonstrated significant efficacy in the MEDALIST trial, achieving transfusion independence in patients with refractory myelodysplastic syndromes.

Decitabine/cedazuridine, approved in July 2020, acts as a nucleoside metabolic inhibitor and showed comparable safety and efficacy to IV decitabine in the ASCERTAIN study, making it a viable treatment option for patients with intermediate or high-risk myelodysplastic syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents for myelodysplastic syndromes. Xu, K., Hansen, E.[2022]

Citations

1. icer.org icer.org/wp-content/uploads/2024/08/MDS_Final-Report_For-Publication_08222024.pdf

Imetelstat for Anemia in Myelodysplastic Syndrome An indirect comparison for the primary endpoint of 8-week transfusion independence after 52 weeks of treatment with imetelstat and 48 weeks of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666634024000345

Imetelstat: Finally a disease-modifying treatment for lower- ... Patients reaching the primary endpoint of 8-week TI showed a median hemoglobin rise of 3.6 g/dL. Clinical success was irrespective of the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11623864/

Imetelstat (Rytelo): a promising treatment for adults with ... Imetelstat can improve overall hemopoiesis and achieve sustained transfusion independence, which might contribute to a reduction in several comorbidities.

4. jmcp.org jmcp.org/doi/full/10.18553/jmcp.2024.30.12.1479

Imetelstat for anemia in lower-risk myelodysplastic ... Forty percent (n = 47) of the 118 participants treated with imetelstat achieved at least 8 weeks of transfusion independence compared with 15% ( ...

5. ir.geron.com ir.geron.com/investors/press-releases/press-release-details/2024/Geron-Announces-New-IMerge-Analyses-Presented-at-ASH-Suggesting-Clinical-Activity-of-RYTELO-imetelstat-in-Patients-with-Lower-Risk-MDS-Regardless-of-Type-or-Number-of-Prior-Therapies/default.aspx

Geron Announces New IMerge Analyses Presented at ASH ... The IMerge data presented at ASH suggesting clinical activity of imetelstat regardless of prior therapies, offers physicians important clinical ...

6. ir.geron.com ir.geron.com/investors/press-releases/press-release-details/2025/Geron-Announces-Presentations-at-ASCO-and-EHA-Underscoring-RYTELO-imetelstat-Efficacy-and-Safety-Across-Range-of-LR-MDS-Patients-and-Showcasing-Momentum-of-Myelofibrosis-Program/default.aspx

Geron Announces Presentations at ASCO and EHA ... Geron Announces Presentations at ASCO and EHA Underscoring RYTELO® (imetelstat) Efficacy and Safety Across Range of LR-MDS Patients, and ...

7. ashpublications.org ashpublications.org/blood/article/145/5/469/525989/Imetelstat-a-new-addition-to-the-therapeutic

a new addition to the therapeutic landscape of lower-risk MDS Imetelstat was considered safe, with transient cytopenias and improvement in patient-reported fatigue. Further studies are required to clearly ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39989126/

Examining the safety and efficacy of imetelstat in low-risk ... This review summarizes promising emerging strategies using imetelstat for the treatment of lower-risk MDS.