Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ruxolitinib in Thrombocythemia and Polycythemia Vera

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04644211
Recruitment Status : Not yet recruiting
First Posted : November 25, 2020
Last Update Posted : November 25, 2020
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Gabriela Hobbs, Massachusetts General Hospital

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.


Condition or disease Intervention/treatment Phase
Essential Thrombocythemia Polycythemia Vera Drug: Ruxolitinib Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study Of Ruxolitinib In Low-Risk Essential Thrombocythemia And Polycythemia Vera With Significant Symptom Burden
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2023


Arm Intervention/treatment
Experimental: 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.
Drug: Ruxolitinib
Pill taken by mouth.
Other Name: Jakafi

Experimental: 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.
Drug: Ruxolitinib
Pill taken by mouth.
Other Name: Jakafi




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Proportion of patients achieving complete hematologic rate at week 12 [ Time Frame: Week 12 ]
    Evaluate the efficacy of ruxolitinib in improving hematologic remission rates, as measured by International Working Group (IWG) working criteria ET: Platelet count ≤ 400 x 109/L, WBC count <10 x 109/L, and absence of leukoerythroblastosis PV: hematocrit <45% and WBC count <10 x 109/L

  2. Proportion of patients achieving complete hematologic rate at 24 Weeks [ Time Frame: Week 24 ]
    Evaluate the efficacy of ruxolitinib in improving hematologic remission rates, as measured by International Working Group (IWG) working criteria ET: Platelet count ≤ 400 x 109/L, WBC count <10 x 109/L, and absence of leukoerythroblastosis PV: hematocrit <45% and WBC count <10 x 109/L

  3. Best MPN-SAF TSS score [ Time Frame: 12 Weeks ]
    Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) for 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. Scale title includes absence of symptom (0) and worst imaginable symptoms (10) per question, with minimum score 0 and maximum score 100. Higher scores indicate worse outcomes.

  4. Best MPN-SAF TSS score [ Time Frame: 24 Weeks ]
    Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) for 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. . Scale title includes absence of symptom (0) and worst imaginable symptoms (10) per question, with minimum score 0 and maximum score 100. Higher scores indicate worse outcomes.

  5. Percentage of change in Spleen Volume [ Time Frame: baseline to 12 weeks ]
    Spleen volume reduction will be measured as the change in percentage spleen volume from baseline at 12 weeks as measured by CT, or MRI in patients with medical contraindication to CT. Summary statistics will be used to describe changes in spleen volume. Volume will be calculated by a computer-assisted perimeter method based on Sorenson et al. Spleen and liver volume will be obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares

  6. Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0 [ Time Frame: All patients who initiate treatment with study drug up to 60 months ]
    descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis essential thrombocythemia (Cohort 1) or polycythemia vera (Cohort 2) 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.1 Patients with polycythemia vera must be low risk (no history of thrombosis and age <60) by NCCN guidelines
  • Patients with an MPN-SAF TSS 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 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, in which case there will be a wash-out period of one week from prior therapy discontinuation to ruxolitinib initiation. Patients who temporarily required cytoreductive therapy for pre-operative control of blood counts prior to surgery are also eligible.
  • 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
    • total bilirubin ≤ institutional upper limit of normal (ULN)
    • AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
    • creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2
  • Participants with a prior or concurrent malignancy not receiving treatment for concurrent cancer diagnosis and/or prior concurrent malignancy within 5 years except for basal cell carcinoma or squamous cell carcinoma of the skin
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • For participants with evidence of chronic human immunodeficiency virus (HIV) infection, they must be negative for HBV DNA, HCV RNA, or hepatitis B surface antigen (BsAg) on suppressive therapy, if indicated.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Ability to understand and the willingness to sign a written informed consent document.

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.
  • 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 inhibitors or inducers of 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.
  • The effects of ruxolitinib on the developing human fetus are unknown. Pregnant women and subjects of childbearing potential who are unwilling to take appropriate precautions to avoid becoming pregnant or fathering a child are ineligible. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ruxolitinib administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04644211


Contacts
Layout table for location contacts
Contact: Gabriela Hobbs, MD (617) 726-8748 ghobbs@partners.org

Locations
Layout table for location information
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Contact: Gabriela Hobbs, MD    617-726-8748    ghobbs@partners.org   
Principal Investigator: Gabriela Hobbs, MD         
Beth-Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Contact: Jeffrey Zwicker, MD    617-667-9920    jwicker@bidmc.harvard.edu   
Principal Investigator: Jeffrey Zwicker, MD         
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Contact: Marlise Luskin, MD    617-632-1906    Marlise_Luskin@DFCI.HARVARD.EDU   
Principal Investigator: Marlise Luskin, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Incyte Corporation
Investigators
Layout table for investigator information
Principal Investigator: Gabriela Hobbs, MD Massachusetts General Hospital
Layout table for additonal information
Responsible Party: Gabriela Hobbs, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04644211    
Other Study ID Numbers: 20-364
First Posted: November 25, 2020    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gabriela Hobbs, Massachusetts General Hospital:
Essential Thrombocythemia
Polycythemia Vera
Sympton Burden
Additional relevant MeSH terms:
Layout table for MeSH terms
Polycythemia Vera
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders