Imetelstat + Ruxolitinib for Myelofibrosis
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Geron Corporation
Must be taking: Ruxolitinib
Must not be taking: JAK inhibitors, Hydroxyurea
Disqualifiers: HIV, Cardiovascular disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Do I have to stop taking my current medications for the trial?
The trial does not specify if you need to stop taking your current medications, but you cannot have taken any investigational drugs, hydroxyurea, chemotherapy, immunomodulatory or immunosuppressive therapy, or high-dose corticosteroids within 14 days before enrolling.
What data supports the effectiveness of the drug combination Imetelstat and Ruxolitinib for treating myelofibrosis?
Research shows that Imetelstat improved overall survival in myelofibrosis patients who had stopped responding to other treatments, with a median survival of 30 months compared to 12 months for those on other therapies. Ruxolitinib has been shown to improve symptoms and quality of life in myelofibrosis patients, making the combination potentially beneficial.
12345Is the combination of Imetelstat and Ruxolitinib safe for treating myelofibrosis?
Ruxolitinib, used for myelofibrosis, has been studied for over a decade and is generally safe, though it can cause anemia (low red blood cell count) and thrombocytopenia (low platelet count). These side effects are usually manageable and rarely lead to stopping treatment.
23467How is the drug combination of Imetelstat and Ruxolitinib unique for treating myelofibrosis?
The combination of Imetelstat and Ruxolitinib is unique because Imetelstat, a telomerase inhibitor, has shown to significantly improve overall survival in patients with myelofibrosis who have not responded to other treatments, like Ruxolitinib alone, which is a common JAK inhibitor. This combination offers a novel approach for patients with limited options after JAK inhibitor failure.
1891011Eligibility Criteria
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.Inclusion Criteria
I can take care of myself and am up and about more than half of my waking hours.
Participants should follow protocol defined contraceptives procedures
A woman of childbearing potential must have a negative serum or urine pregnancy test at screening
+7 more
Exclusion Criteria
I have HIV or a severe infection needing IV antibiotics.
Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%
I have had surgery to remove all or part of my spleen.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Part 1
Participants who have received ruxolitinib for at least 12 weeks prior to Screening will initiate imetelstat therapy. Dose levels of imetelstat may include 4.7, 6, 7.5, 9.4mg, until a RP2D is established.
24 weeks
Regular visits for dose adjustments and monitoring
Treatment Part 2
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.
24 weeks
Regular visits for monitoring and assessment
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days after the last dose
Participant Groups
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.
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.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of HopeDuarte, CA
Icahn School of Medicine at Mount SinaiNew York, NY
Texas OncologyTyler, TX
H. Lee Moffitt Cancer Center and Research Institute, Inc.Tampa, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Geron CorporationLead Sponsor
References
Favorable overall survival with imetelstat in relapsed/refractory myelofibrosis patients compared with real-world data. [2022]In the MYF2001 trial, treatment of Janus kinase (JAK) inhibitor-relapsed/refractory intermediate-2 or high-risk myelofibrosis (MF) with imetelstat 9.4 mg/kg every 3 weeks demonstrated encouraging median overall survival of 29.9 months. To provide historical context, external real-world data (RWD) were collected from a study of 96 patients who had discontinued ruxolitinib and were subsequently treated with best available therapy (BAT) at Moffitt Cancer Center. A closely matched cohort was identified using the MYF2001 eligibility criteria, including patients with MF who had discontinued ruxolitinib due to lack or loss of response. Overall survival was measured from time of JAK inhibitor discontinuation to death or censored at last follow-up. To improve comparability, propensity score weighting approaches using average treatment effect for overlap population (ATO) and stabilized inverse probability treatment weighting (sIPTW) were used for 10 critical baseline covariates. Fifty-seven patients treated with imetelstat 9.4 mg/kg from MYF2001 and 38 patients treated with BAT from RWD were analyzed with improved balanced baseline covariates after propensity score adjustment, showing significantly lower risk of death with imetelstat compared with BAT (hazard ratio: 0.35; p = 0.0019). With sIPTW, results were similar. Results of sensitivity analyses were consistent with the primary analysis. In conclusion, treatment with imetelstat was associated with longer overall survival compared to BAT (30 vs 12 months, respectively) in closely matched patients with MF after JAK inhibitor failure, warranting further evaluation of imetelstat in this poor-prognosis patient population.
Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. [2021]Patients with myelofibrosis (MF) have significant debilitating symptoms, physical disabilities, and poor health-related quality of life (HRQoL). Here, we report post-hoc analyses of the impact of ruxolitinib, a potent and selective JAK1 and JAK2 inhibitor, on disease-related symptoms and HRQoL in MF patients from the large phase 3 COMFORT-II study (N = 219). During the follow-up period of 48 weeks, HRQoL and MF-associated symptoms improved from baseline for ruxolitinib-treated patients but remained the same or worsened for best available therapy (BAT)-treated patients. Based on the European Organization for Research and Treatment of Cancer QoL Questionnaire core 30 items (EORTC QLQ-C30), treatment-induced differences in physical and role functioning, fatigue, and appetite loss significantly favoured ruxolitinib versus BAT from week 8 (P
Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts
JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. [2022]Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis.
Management of Myelofibrosis during Treatment with Ruxolitinib: A Real-World Perspective in Case of Resistance and/or Intolerance. [2022]The development and approval of ruxolitinib, the first JAK1/2 inhibitor indicated to treat myelofibrosis, has improved patient outcomes, with higher spleen and symptoms responses, improved quality of life, and overall survival. Despite this, several unmet needs remain, including the absence of resistance criteria, suboptimal response, the timing of allogeneic transplant, and the management of patients in case of intolerance. Here, we report the results of the second survey led by the "MPN Lab" collaboration, which aimed to report physicians' perspectives on these topics. As in our first survey, physicians were selected throughout Italy, and we included those with extensive experience in treating myeloproliferative neoplasms and those with less experience representing clinical practice in the real world. The results presented here, summarized using descriptive analyses, highlight the need for a clear definition of response to ruxolitinib as well as recommendations to guide the management of ruxolitinib under specific conditions including anemia, thrombocytopenia, infections, and non-melanoma skin cancers.
Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. [2021]Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded-access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109 /l) and patients without splenomegaly - populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low-platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low-platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non-haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50-100 × 109 /l. (ClinicalTrials.gov identifier NCT01493414).
Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. [2023]Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.
Fedratinib: a pharmacotherapeutic option for JAK-inhibitor naïve and exposed patients with myelofibrosis. [2022]Ruxolitinib is the most commonly used JAK-inhibitor (JAKi) for the management of symptoms related to splenomegaly and cytokine-mediated inflammation in patients with myelofibrosis (MF), but is limited by variable durability of response with most patients experiencing failure after 2-3 years. Long-term data on other approved JAKi, fedratinib and pacritinib, are not available due to the clinical hold put on pivotal trials for toxicity concerns.
Ruxolitinib is manageable in patients with myelofibrosis and severe thrombocytopenia: a report on 12 Danish patients. [2021]We report 12 Danish myelofibrosis patients who have been treated successfully with ruxolitinib despite having low platelet counts (
A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. [2021]Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib.
Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis. [2021]Patients with myelofibrosis who are relapsed or refractory (R/R) to Janus-associated kinase inhibitors (JAKis) have poor clinical outcomes including dismal overall survival (OS) that ranges between 13 and 16 months. Imetelstat, a telomerase inhibitor, was evaluated in patients with intermediate-2 or high-risk myelofibrosis R/R to JAKi in a phase II multicenter study (ClinicalTrials.gov identifier: NCT02426086).