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Ruxolitinib in Thrombocythemia and Polycythemia Vera

Primary Purpose

Essential Thrombocythemia, Polycythemia Vera

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Essential Thrombocythemia focused on measuring Essential Thrombocythemia, Polycythemia Vera, Sympton Burden

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Massachusetts General HospitalRecruiting
  • Beth-Israel Deaconess Medical Center
  • Dana Farber Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Ruxolitinib Stage 1

Ruxolitinib Stage 2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Percentage of patients who achieve >50% reduction from baseline to Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score
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

Proportion of patients achieving complete hematologic rate at 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
Proportion of patients achieving complete hematologic rate at 24 Weeks
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
Best MPN-SAF TSS score
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.
Best MPN-SAF TSS score
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.
Percentage of change in Spleen Volume
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
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
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

Full Information

First Posted
November 10, 2020
Last Updated
October 21, 2022
Sponsor
Massachusetts General Hospital
Collaborators
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04644211
Brief Title
Ruxolitinib in Thrombocythemia and Polycythemia Vera
Official Title
A Phase 2 Study Of Ruxolitinib In Low-Risk Essential Thrombocythemia And Polycythemia Vera With Significant Symptom Burden
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2022 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Thrombocythemia, Polycythemia Vera
Keywords
Essential Thrombocythemia, Polycythemia Vera, Sympton Burden

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ruxolitinib Stage 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Ruxolitinib Stage 2
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi
Intervention Description
Pill taken by mouth.
Primary Outcome Measure Information:
Title
Percentage of patients who achieve >50% reduction from baseline to Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score
Description
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
Time Frame
baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients achieving complete hematologic rate at week 12
Description
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
Time Frame
Week 12
Title
Proportion of patients achieving complete hematologic rate at 24 Weeks
Description
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
Time Frame
Week 24
Title
Best MPN-SAF TSS score
Description
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.
Time Frame
12 Weeks
Title
Best MPN-SAF TSS score
Description
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.
Time Frame
24 Weeks
Title
Percentage of change in Spleen Volume
Description
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
Time Frame
baseline to 12 weeks
Title
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
Description
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
Time Frame
All patients who initiate treatment with study drug up to 60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriela Hobbs, MD
Phone
(617) 726-8748
Email
ghobbs@partners.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriela Hobbs, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriela Hobbs, MD
Phone
617-726-8748
Email
ghobbs@partners.org
First Name & Middle Initial & Last Name & Degree
Gabriela Hobbs, MD
Facility Name
Beth-Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeffrey Zwicker, MD
Phone
617-667-9920
Email
jwicker@bidmc.harvard.edu
First Name & Middle Initial & Last Name & Degree
Jeffrey Zwicker, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marlise Luskin, MD
Phone
617-632-1906
Email
Marlise_Luskin@DFCI.HARVARD.EDU
First Name & Middle Initial & Last Name & Degree
Marlise Luskin, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication
IPD Sharing Access Criteria
Contact the Partners Innovations team at http://www.partners.org/innovation

Learn more about this trial

Ruxolitinib in Thrombocythemia and Polycythemia Vera

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