A Phase 2 Study Of Ruxolitinib In Low-Risk Essential Thrombocythemia And Polycythemia Vera With Significant Symptom Burden
Overview
- Phase
- Phase 2
- Intervention
- Ruxolitinib
- Conditions
- Essential Thrombocythemia
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 60
- Locations
- 7
- Primary Endpoint
- Percentage of patients who achieve >50% reduction from baseline to Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This research is being done to see if the drug ruxolitinib is effective in reducing the symptoms caused by low-risk essential thrombocythemia (ET) and polycythemia vera (PV).
- This research study involves the study drug Ruxolitinib.
Detailed Description
This is a multi-center, non-randomized, two-stage phase II clinical trial evaluating ruxolitinib in low-risk but symptomatic essential thrombocythemia (ET) and polycythemia vera (PV) patients. This research is being done to see if Ruxolitinib is effective in reducing the symptoms people with essential thrombocythemia (ET) and polycythemia vera (PV) are experiencing. Ruxolitinib is a type of drug that blocks the specific proteins that may be causing the symptoms people with essential thrombocythemia (ET) and polycythemia vera (PV are experiencing. The research study procedures include screening for eligibility and study treatment, including evaluations and follow up visits. \- Participants will receive Ruxolitinib for approximately 6 months and if benefitting from it may continue to receive Ruxolitinib for as long as there is no unacceptable side effects or disease progression. It is expected that about 60 people will take part in this research study. The U.S. Food and Drug Administration (FDA) has approved Ruxolitinib for polycythemia vera (PV) but not for people with essential thrombocythemia (ET) and polycythemia vera (PV). Incyte, a biopharmaceutical company, is supporting this research study by providing funding for the study, including the study drug.
Investigators
Gabriela Hobbs
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Patients who have been diagnosed with essential thrombocythemia or polycythemia vera by World Health Organization 2016 diagnostic criteria.
- •Patients with essential thrombocythemia must be very low (no history of thrombosis, age \<60, and no JAK2 mutation), low (no history of thrombosis, age \<60, presence of JAK2 mutation), or intermediate risk (no history of thrombosis, age \>60, no JAK2 mutation) by IPSET criteria. Patients with polycythemia vera must be low risk (no history of thrombosis and age \<60) by NCCN guidelines.
- •Patients with an MPN-SAF TSS (MPN-10) score \>10 AND at least one individual feature \>5 documented on a separate visit within 3 months prior to study registration, as documented in the clinical record or obtained by clinician. If not previously documented in the electronic medical record, participants must be blinded to purpose of MPN SAF TSS scoring for eligibility determination. Average daily MPN-SAF TSS (MPN-10) score must remain \>10 with any individual feature \>5 for the week-long baseline assessment prior to ruxolitinib initiation.
- •Patients who have previously received or are receiving cytoreductive therapy (i.e. hydroxyurea, anagrelide, interferon) are eligible for the study if therapy was used for the indication of symptom control, or if therapy was used for pre-operative control of blood counts. If a subject is still receiving cytoreductive therapy at the time of screening and enrollment, there will be a wash-out period from prior cytoreductive therapy at least 7 days prior to ruxolitinib initiation.
- •Age ≥18 years.
- •ECOG performance status ≤2 (Karnofsky ≥60%)
- •Participants must have adequate organ and marrow function as defined below:
- •leukocytes ≥3,000/mcL
- •absolute neutrophil count ≥1,500/mcL
- •platelets ≥100,000/mcL
Exclusion Criteria
- •Essential thrombocythemia patients who are high risk by IPSET-R criteria (age \> 60 with JAK2 V617F mutation and/or history of thrombosis).1 Polycythemia vera patients who are high risk by NCCN guidelines (age \> 60 and/or history of thrombosis).
- •Patients with \>5% blasts on baseline marrow exam or at any other time in peripheral blood
- •Participants who are receiving any other investigational agents.
- •Participants with a history of splenectomy. Participants may still be eligible after discussion with and approval by the Overall PI, however.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or excipients of ruxolitinib.
- •Participants requiring any medications or substances that are strong inhibitors or 3A4 isozyme are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
- •Participants with uncontrolled intercurrent illness.
- •Participants with inadequate liver or renal function at screening as evidenced by lab values not meeting criteria
- •Participants with psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because ruxolitinib is a Class C agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib.
Arms & Interventions
Ruxolitinib Stage 1
In stage 1, participants will be divided into two cohorts: * Very low, Low, and Intermediate-risk ETpatients with significant symptom burden and Low-risk PV patients with significant symptom burden * Study cycles are 28 days long, participants in both cohorts will receive: * Ruxolitinib 2x daily for 6 study cycles.
Intervention: Ruxolitinib
Ruxolitinib Stage 2
Stage 2 will commence based on 3 or more participants in Stage 1 showing a predetermined positive response to Ruxolitinib. In stage 2, participants will be divided into two cohorts: * Very low, Low, and Intermediate-risk ET patients with significant symptom burden and Low-risk PV patients with significant symptom burden * Study cycles are 28 days long, participants in both cohorts will receive: * Ruxolitinib 2x daily for 6 study cycles.
Intervention: Ruxolitinib
Outcomes
Primary Outcomes
Percentage of patients who achieve >50% reduction from baseline to Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score
Time Frame: baseline to 12 weeks
Percentage of patients with \>50% change in Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS), which has use in major clinical trials and as symptom assessment in all patients in clinical practice. Modeling has established baseline MPN-SAF TSS cut-off scores (total MPN-SAF TSS \>20 or an individual component score \>5) at which symptomatic treatment would be significantly beneficial
Secondary Outcomes
- Best MPN-SAF TSS score(24 Weeks)
- Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0(All patients who initiate treatment with study drug up to 60 months)
- Percentage of change in Spleen Volume(baseline to 12 weeks)
- Proportion of patients achieving complete hematologic rate at 24 Weeks(Week 24)
- Proportion of patients achieving complete hematologic rate at week 12(Week 12)
- Best MPN-SAF TSS score(12 Weeks)