Imetelstat for Myelodysplastic Syndrome

Recruiting at 148 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

289 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of imetelstat sodium in transfusion-dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment in Phase 2 study and to compare the efficacy, in terms of red blood cell (RBC) transfusion independence (TI), of imetelstat sodium to placebo in transfusion-dependent participants with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment in Phase 3 study. A separate Ventricular Repolarization Substudy (QTc Substudy) will evaluate the effect of imetelstat sodium on ventricular repolarization. An Extension Phase has been included to allow continued treatment for those participants who are benefitting from imetelstat sodium and to continue to evaluate the long-term safety, overall survival (OS), and disease progression, including progression to acute myeloid leukemia (AML) in transfusion-dependent participants with low or immediate-1 risk MDS that is relapsed/refractory to ESA treatment.

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).

What data supports the effectiveness of the drug Imetelstat for treating myelodysplastic syndrome?

Imetelstat has shown promising results in clinical trials for patients with lower-risk myelodysplastic syndromes who are dependent on red blood cell transfusions and do not respond to other treatments. It has been reported to help some patients achieve independence from transfusions, which is a significant improvement for those with limited treatment options. ^{1 2 3 4 5}

Is Imetelstat safe for humans?

Imetelstat has been studied in patients with myeloproliferative neoplasms and myelodysplastic syndromes, showing some side effects like thrombocytopenia (low platelet count), which can affect blood clotting. However, it has shown promising results in treating these conditions, indicating it is generally safe for use in humans with careful monitoring. ^{1 2 6 7 8}

How is the drug Imetelstat different from other treatments for myelodysplastic syndrome?

Imetelstat is unique because it is a telomerase inhibitor, which means it targets and blocks the enzyme telomerase that cancer cells use to keep dividing. This is different from other treatments that often focus on stimulating blood cell production or targeting other pathways. ^{1 2 5 7 8}

Research Team

Tymara Berry, MD

Principal Investigator

Geron Corporation

Eligibility Criteria

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 am 18 years old or older.

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Evolving therapies for lower-risk myelodysplastic syndromes. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

MDS: Refining existing therapy through improved biologic insights. [2012]

4. England pubmed.ncbi.nlm.nih.gov

Updates on risk stratification and management of lower-risk myelodysplastic syndromes/neoplasms. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Imetelstat Achieves Meaningful and Durable Transfusion Independence in High Transfusion-Burden Patients With Lower-Risk Myelodysplastic Syndromes in a Phase II Study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Novel agents for myelodysplastic syndromes. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Imetelstat, a telomerase inhibitor, differentially affects normal and malignant megakaryopoiesis. [2018]