Imetelstat for Myelofibrosis

Recruiting at 281 trial locations

Overseen By Michelle Mudge-Riley, DO

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Geron Corporation

Must be taking: JAK-inhibitors

Must not be taking: Chemotherapy, Corticosteroids, others

Disqualifiers: High blood blast count, Malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 22

Duration: Up to 3 years

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a drug called imetelstat works compared to other available treatments for people with myelofibrosis (a type of bone marrow cancer) who haven't responded well to JAK-inhibitor treatments. The main goal is to determine if imetelstat can help patients live longer. Participants will receive either imetelstat or the best available therapy (BAT) chosen by doctors. This trial might suit someone with intermediate-2 or high-risk myelofibrosis who has tried JAK-inhibitors without improvements in spleen size or symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to access a potentially life-extending treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any chemotherapy or myelofibrosis-directed therapy, including JAK-inhibitors, at least 14 days before starting the study. Other medications may need to be stopped as well, but the protocol does not specify all details.

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

Research has shown that imetelstat, the treatment under study, is generally well-tolerated by patients with myelofibrosis. In earlier studies, anemia (a low red blood cell count) affected 42% of patients, and thrombocytopenia (a low platelet count) affected 41%. Additionally, 37% of patients reported diarrhea.

Another study combined imetelstat with a different drug and found no dose-limiting toxicities, indicating that patients could handle the treatment well at the given doses. This suggests that imetelstat maintains a consistent safety profile, with predictable and manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myelofibrosis?

Imetelstat is unique because it targets the telomerase enzyme, a critical component in cancer cell survival, which is a different approach compared to most treatments for myelofibrosis that focus on managing symptoms with JAK inhibitors. Researchers are excited about imetelstat because it directly interferes with the cancer cell's ability to multiply, offering a potential new way to slow or stop disease progression. Additionally, its administration via intravenous infusion every 21 days could provide a more manageable treatment schedule for patients compared to daily oral medications.

What evidence suggests that this trial's treatments could be effective for Myelofibrosis?

Research shows that imetelstat, one of the treatments in this trial, may help treat myelofibrosis, a type of bone marrow cancer. Studies found that people treated with imetelstat at a dose of 9.4 mg/kg lived for a median of about 30 months. Additionally, around 40.5% of patients experienced improvements in their bone marrow condition, which is crucial for those with myelofibrosis. The one-year survival rate for patients using imetelstat was about 81%, indicating its potential effectiveness. Imetelstat is already approved for treating another condition called lower-risk myelodysplastic syndromes, supporting its safety and effectiveness. Participants in this trial may receive imetelstat or the Best Available Therapy (BAT), which serves as an active comparator. ^{1 2 6 7 8}

Who Is on the Research Team?

Faye Feller

Principal Investigator

Geron Corporation

Are You a Good Fit for This Trial?

This trial is for adults with intermediate-2 or high-risk Myelofibrosis who haven't improved after treatment with JAK-inhibitor drugs. They should not be eligible for a stem cell transplant, have symptoms of MF, and meet certain blood test criteria. People can't join if they've had recent major surgery, other cancers (with some exceptions), uncontrolled infections, liver disease unrelated to MF, or previous imetelstat treatment.

Inclusion Criteria

Participants should follow protocol defined contraceptives procedures

A woman of childbearing potential must have a negative serum or urine pregnancy test at screening

My spleen has grown after JAK inhibitor treatment and I can't have more of this treatment.

Exclusion Criteria

I have no active cancer except for treated skin cancer or cervical carcinoma in situ.

I haven't taken any cancer drugs, steroids over 30 mg/day, or JAK inhibitors in the last 14 days.

I have HIV or a current severe infection needing IV antibiotics.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive imetelstat or best available therapy until disease progression or unacceptable toxicity

Up to 3 years

Every 21 days (±3 days) for imetelstat group

Follow-up

Participants are monitored for safety and effectiveness after treatment

Until death, lost to follow-up, withdrawal of consent, or study end

Crossover

Participants on BAT who meet progressive disease criteria may crossover to receive imetelstat treatment

What Are the Treatments Tested in This Trial?

Interventions

• Best Available Therapy (BAT)
• Imetelstat

Trial Overview The study compares the effectiveness of Imetelstat versus Best Available Therapy (BAT) in improving overall survival rates in patients whose Myelofibrosis hasn't responded to JAK-inhibitors. Participants will either receive Imetelstat or their doctor's choice of another therapy deemed best available.

How Is the Trial Designed?

Group I: Imetelstat Experimental Treatment 1 Intervention

Participants will receive imetelstat sodium at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Group II: Best Available Therapy (BAT) Active Control 1 Intervention

Participants will receive BAT (investigator-selected non-JAK-inhibitor treatment), until disease progression or unacceptable toxicity, treatment discontinuation or study end. Participants on BAT who meet protocol-defined criteria for progressive disease may crossover to receive imetelstat treatment after sponsor's approval.

Who Is Running the Clinical Trial?

Geron Corporation

Lead Sponsor

Trials

20

Recruited

1,500+

Published Research Related to This Trial

Imetelstat, a telomerase inhibitor, showed significant clinical benefits in a Phase II study for patients with myelofibrosis who did not respond to JAK inhibitors, indicating its potential as a new treatment option.

The ongoing Phase III trial (IMpactMF) aims to evaluate imetelstat's effectiveness compared to the best available therapy, focusing on overall survival and various secondary outcomes, with a dosing regimen of 9.4 mg/kg every 21 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imetelstat in intermediate-2 or high-risk myelofibrosis refractory to JAK inhibitor: IMpactMF phase III study design. Mascarenhas, J., Harrison, CN., Kiladjian, JJ., et al.[2022]

In the MYF2001 trial, patients with relapsed or refractory myelofibrosis treated with imetelstat showed a median overall survival of 29.9 months, indicating its potential efficacy in this challenging condition.

When compared to best available therapy (BAT) in a closely matched cohort, imetelstat significantly reduced the risk of death (hazard ratio: 0.35), suggesting it may offer a substantial survival advantage over traditional treatments after JAK inhibitor failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable overall survival with imetelstat in relapsed/refractory myelofibrosis patients compared with real-world data. Kuykendall, AT., Sun, L., Mascarenhas, J., et al.[2022]

In a phase 3 trial involving 156 patients with myelofibrosis who had previously been treated with ruxolitinib, momelotinib did not show superior efficacy compared to best available therapy (BAT) in reducing spleen size by at least 35%.

Both momelotinib and BAT had similar rates of severe adverse events, but momelotinib was associated with a higher incidence of peripheral neuropathy and serious adverse events, including deaths, indicating potential safety concerns with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Harrison, CN., Vannucchi, AM., Platzbecker, U., et al.[2021]

JAK inhibitors like ruxolitinib have significantly improved symptoms and quality of life for myelofibrosis patients, particularly by reducing spleen size, but they do not consistently lead to molecular or pathological improvements in the disease.

Despite their benefits, over half of patients discontinue JAK inhibitor treatment within 3 years due to side effects like cytopenias and neuropathy, highlighting the need for better strategies for patients who do not respond to these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat myelofibrosis after failure of JAK inhibitors. Pardanani, A., Tefferi, A.[2021]

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]

Momelotinib, a JAK inhibitor, is being evaluated for its efficacy and safety in treating myelofibrosis, a disorder that can range from mild to severe symptoms, including significant splenomegaly and the need for blood transfusions.

The review highlights the advancements in treatment options for myelofibrosis and positions momelotinib as a promising candidate in the evolving therapeutic landscape for this condition as of 2020.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Safety, Efficacy, and Therapeutic Potential of Momelotinib in the Treatment of Intermediate/High-Risk Myelofibrosis: Evidence to Date. Bassiony, S., Harrison, CN., McLornan, DP.[2020]

In a phase II study involving patients with myelofibrosis who were resistant to JAK inhibitors, the higher dose of imetelstat (9.4 mg/kg) showed significant clinical benefits, including a median overall survival of 29.9 months and improved spleen and symptom response rates compared to the lower dose (4.7 mg/kg).

Imetelstat treatment led to notable improvements in bone marrow fibrosis and reductions in driver mutation frequencies, indicating its potential effectiveness in targeting the underlying disease mechanisms, while maintaining an acceptable safety profile with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis. Mascarenhas, J., Komrokji, RS., Palandri, F., et al.[2021]

Ruxolitinib, a JAK1/JAK2 inhibitor, has significantly improved the management of myelofibrosis, but it has limitations such as myelosuppression and loss of response, leading to the need for additional treatment options.

Newly approved JAK inhibitors like fedratinib and pacritinib provide effective alternatives for patients, especially those with severe thrombocytopenia and those who have lost response to ruxolitinib, while momelotinib shows promise in treating anemia, indicating a growing arsenal of therapies for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition in myelofibrosis: how to sequence treatment in this new era of multiple options. Stein, BL.[2023]

JAK inhibitors have significantly improved treatment options for myelofibrosis (MF) by alleviating symptoms, reducing spleen size, and enhancing quality of life, although they may lead to worsening blood cell counts (cytopenias).

Despite their benefits, JAK inhibitors do not stop disease progression or prevent the transformation to leukemia, and their impact on overall survival remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors in the treatment of myelofibrosis. Levavi, H., Hoffman, R., Marcellino, BK.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18593

Outcomes with imetelstat in myelofibrosis: A systematic ... The pooled overall survival (OS) at 1 year, as reported by two studies, was 80.95% (95% CI: 74.95-86.93, p=0.54, I²=0.0%). The median pooled OS ...

2. 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 ... “While imetelstat is already playing a vital role in LR-MDS, these new analyses being presented at ASCO and EHA reinforce its potential to give ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34138638/

Randomized, Single-Blind, Multicenter Phase II Study of ... Treatment with imetelstat 9.4 mg/kg led to a median OS of 29.9 months and bone marrow fibrosis improvement in 40.5% and variant allele frequency ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04576156

NCT04576156 | A Study Comparing Imetelstat Versus Best ... The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 ...

5. onclive.com onclive.com/view/improvemf-trial-shows-early-potential-of-imetelstat-plus-ruxolitinib-in-myelofibrosis

IMproveMF Trial Shows Early Potential of Imetelstat Plus ... Imetelstat is already an approved drug for transfusion-dependent, lower-risk MDS based on the phase 3 IMerge trial [NCT02598661]. It has clear ...

6. onclive.com onclive.com/view/imetelstat-plus-ruxolitinib-demonstrates-tolerable-safety-profile-in-myelofibrosis

Imetelstat Plus Ruxolitinib Demonstrates Tolerable Safety ... The combination of imetelstat and ruxolitinib showed a consistent safety profile with no dose-limiting toxicities in myelofibrosis patients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11571238/

Imetelstat, a novel, first‐in‐class telomerase inhibitor Overall, results from the E‐R analyses confirmed the clinical outcomes of IMbark/MYF2001 showing better clinical benefit of imetelstat 8.9 mg/kg ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01731951

NCT01731951 | Imetelstat Sodium in Treating Participants ... This pilot clinical trial studies how well imetelstat sodium works in treating participants with primary or secondary myelofibrosis and other myeloid ...