What side effects are associated with this type of intervention?

Imetelstat, a telomerase inhibitor, can cause side effects such as fatigue, gastrointestinal disturbances (nausea, diarrhea), cytopenias (anemia, thrombocytopenia, neutropenia), and liver function abnormalities. Ruxolitinib, a JAK1/2 inhibitor, is commonly associated with side effects including anemia, thrombocytopenia, bruising, dizziness, headaches, and increased risk of infections. Both treatments require careful monitoring by healthcare providers to manage these potential adverse effects effectively.

What prior FDA approvals exist?

Ruxolitinib, a JAK1/2 inhibitor, has been approved by the FDA for the treatment of Myelofibrosis. It is effective in reducing splenomegaly and symptom burden in patients with this condition. Another drug, Fedratinib, also a JAK2 inhibitor, has been approved for similar indications, showing efficacy in reducing spleen volume and symptom scores. These treatments are similar to the combination being studied in the trial with Imetelstat, a telomerase inhibitor, and Ruxolitinib.

What other types of research exist?

Promising novel alternatives for Myelofibrosis treatment in 2024 include: 1) Fedratinib, a JAK2 inhibitor that has shown efficacy in patients resistant to Ruxolitinib. 2) Pacritinib, another JAK2 inhibitor, particularly beneficial for patients with low platelet counts. 3) Luspatercept, an erythroid maturation agent, which may help manage anemia associated with MF. These alternatives have demonstrated potential in clinical trials and offer new avenues for treatment.

← Back to Search

Telomerase Inhibitor

Imetelstat + Ruxolitinib for Myelofibrosis

Phase 1

Recruiting

Research Sponsored by Geron Corporation

Eligibility Criteria Checklist

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

Must have

Candidate for ruxolitinib treatment: Part 1 participants only must be on ruxolitinib treatment for at least 12 weeks with at least 4 consecutive weeks immediately prior to enrollment at a stable dose. Part 2 participants only must be a candidate for ruxolitinib treatment as assessed by the investigator and has not previously been treated with a JAK inhibitor

Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2

Must not have

Prior history of partial or complete splenectomy

Prior treatment with imetelstat

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from first dose to end of the treatment (up to approximately 5 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, imetelstat and ruxolitinib, in patients with myelofibrosis, a type of bone marrow cancer. Imetelstat works by stopping cancer cells from multiplying, while ruxolitinib slows their growth. The study aims to find the best dose and evaluate the safety and effectiveness of this combination. Ruxolitinib is a targeted drug approved for treating myelofibrosis, known for reducing spleen size and improving survival rates.

Who is the study for?

This trial is for adults with a condition called myelofibrosis, who are either already on ruxolitinib treatment or haven't been treated with JAK inhibitors. They should have symptoms like an enlarged spleen or other related issues and must not be candidates for stem cell transplant. Participants need to meet certain blood and biochemical test criteria, have a performance status score of 0-2, and agree to use contraception.

What is being tested?

The study tests the combination of two drugs: Imetelstat and Ruxolitinib in people with myelofibrosis. The first part determines the best dose of Imetelstat when used with Ruxolitinib, while the second part assesses safety and how well this combined dose works.

What are the potential side effects?

Possible side effects include reactions at the injection site, changes in blood counts leading to increased risk of infections or bleeding, liver problems, fatigue, shortness of breath, gastrointestinal issues such as nausea or diarrhea.

Eligibility Criteria

Inclusion Criteria

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

Select...

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

Select...

I have been diagnosed with a type of myelofibrosis according to specific health criteria.

Select...

My myelofibrosis is classified as intermediate-1, intermediate-2, or high-risk.

Select...

I have symptoms or an enlarged spleen due to myelofibrosis.

Select...

I cannot or do not want to have a stem cell transplant.

Exclusion Criteria

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

Select...

I have had surgery to remove all or part of my spleen.

Select...

I have been treated with imetelstat before.

Select...

I have a serious heart condition.

Select...

I have HIV or a severe infection needing IV antibiotics.

Select...

I have had a stem cell transplant in the past.

Select...

I have been treated with a JAK inhibitor before.

Select...

I am allergic to imetelstat, ruxolitinib, or their ingredients.

Select...

I have not had major surgery in the last 28 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from first dose to end of the treatment (up to approximately 5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from first dose to end of the treatment (up to approximately 5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from first dose to end of the treatment (up to approximately 5 years) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Part 2: Number of Participants With Treatment-emergent Adverse Event (AE)

Part 2: Symptom Response Rate at Week 24

Secondary study objectives

Part 1 and 2: Duration of Response (DOR) Per IWG-MRT Criteria

Part 1 and 2: Progression Free Survival (PFS)

Bone Marrow

+3 more

Side effects data

From 2018 Phase 2 trial • 80 Patients • NCT01731951

100%

Diarrhoea

100%

Neutrophil count decreased

100%

Fatigue

100%

Platelet count decreased

100%

White blood cell count decreased

89%

Anaemia

78%

Hyperglycaemia

56%

Aspartate aminotransferase increased

56%

Pain

56%

Alanine aminotransferase increased

44%

Nausea

44%

Back pain

44%

Blood creatinine increased

33%

Contusion

33%

Lipase increased

33%

Blood bilirubin increased

22%

Constipation

22%

Blood amylase increased

22%

Upper respiratory tract infection

22%

Hypokalaemia

22%

Muscular weakness

22%

Neck pain

22%

Insomnia

22%

Hyperhidrosis

22%

Cough

22%

Cardiac failure

22%

Oedema peripheral

22%

Weight decreased

22%

Anorexia

22%

Decreased appetite

22%

Hypernatraemia

22%

Hypocalcaemia

22%

Hyponatraemia

22%

Dyspnoea

22%

Pain in extremity

22%

Hypertension

22%

Headache

22%

Alopecia

22%

Arthralgia

22%

Weight increased

11%

Sepsis

11%

Lymphocyte count decreased

11%

Atrial fibrillation

11%

Abdominal distension

11%

Night sweats

11%

Dizziness

11%

Anxiety

11%

Early satiety

11%

Vomiting

11%

Lung infection

11%

Infusion related reaction

11%

Pyrexia

11%

Blood alkaline phosphatase increased

11%

Gamma-glutamyltransferase increased

11%

Hyperkalaemia

11%

Hyperuricaemia

11%

Epistaxis

11%

Abdominal pain upper

11%

Non-cardiac chest pain

11%

Fall

11%

Musculoskeletal pain

11%

Pulmonary hypertension

11%

Sinusitis

11%

Hypotension

100%

80%

60%

40%

20%

Study treatment Arm

Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)

Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia

Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts])

Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])

Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)

Arm A: Imetelstat 9.4 mg/kg (MF)

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: Imetelstat + RuxolitinibExperimental Treatment2 Interventions

Part 1: Participants who have received ruxolitinib orally (PO) as part of standard of care (SOC) for at least 12 weeks prior to Screening will be enrolled. After enrollment, participants will initiate imetelstat therapy. Dose levels of imetelstat may include 4.7, 6, 7.5, 9.4mg, until a RP2D is established. Part 2: Janus kinase (JAK) inhibitor naïve participants will receive initial treatment with ruxolitinib for at least 12 weeks, including 4 weeks at a stable dose, followed by imetelstat treatment at the RP2D in combination with ruxolitinib.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Imetelstat

2012

Completed Phase 2

~100

Ruxolitinib

2018

Completed Phase 3

~1170

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

Imetelstat is a telomerase inhibitor that targets the enzyme telomerase, which is often overactive in cancer cells, leading to their uncontrolled proliferation. By inhibiting telomerase, Imetelstat can limit the ability of these cells to replicate, potentially reducing disease progression. Ruxolitinib is a JAK1/2 inhibitor that blocks the Janus kinase pathway, frequently mutated and overactive in Myelofibrosis. This pathway regulates blood cell production and immune function. By inhibiting JAK1/2, Ruxolitinib reduces abnormal signaling, alleviating symptoms and reducing spleen size. These mechanisms are crucial for controlling disease progression and improving quality of life for Myelofibrosis patients.