Back to resultsStudy to Evaluate Safety, Tolerability, and Pharmacokinetics of Idelalisib in Adults Receiving Ruxolitinib as Therapy for Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis With Progressive or Relapsed Disease (Madison)
Primary Purpose
Myelofibrosis
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Idelalisib
Ruxolitinib
Sponsored by
About this trial
This is an interventional treatment trial for Myelofibrosis
Eligibility Criteria
Key Inclusion Criteria:
- Individuals must have been on a stable dose of ruxolitinib for at least 4 weeks prior to study entry
- Individuals with PMF, post-PV MF, or post-ET MF classified as high risk or intermediate risk as defined by the Dynamic International Prognostic Scoring System (DIPSS) for PMF or DIPSS Plus, if cytogenetics are available
- Individuals with PMF, post-PV MF, or post-ET MF who are receiving ruxolitinib and meet 2013 Revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria with progressive and relapsed disease, with modifications for progressive disease complete remission (CR), partial remission (PR), or clinical improvement (CI)
- European Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Required screening laboratory values as described in the protocol
- Willing and able to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions including mandatory prophylaxis for pneumocystis jiroveci pneumonia (PJP)
- Able to understand and willing to sign the informed consent form
Key Exclusion Criteria:
- Individuals on a stable ruxolitinib dose of 5 mg once daily
- History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
- Ongoing drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver
- Ongoing drug-induced pneumonitis
- Ongoing inflammatory bowel disease
- Ongoing alcohol or drug addiction
- Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
- Known hypersensitivity to the study investigational medicinal product (IMP), the metabolites, or formulation excipients
- Unwilling or unable to take oral medication
- Unresolved non-hematologic toxicities from prior therapies that are > Common terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of alopecia [Grade 1 or 2 permitted])
- Pregnant or lactating females
- Cytomegalovirus (CMV): Ongoing infection, treatment, or prophylaxis within the past 28 days
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Sites / Locations
- Stanford Hospital and Clinics
- University of Michigan Health System
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort A, Idelalisib + Ruxolitinib
Cohort B, Idelalisib + Ruxolitinib
Cohort C, Idelalisib + Ruxolitinib
Cohort D, Idelalisib + Ruxolitinib
Arm Description
Idelalisib 50 mg once daily in participants receiving ruxolitinib.
Idelalisib 50 mg twice daily in participants receiving ruxolitinib.
Idelalisib 150 mg once daily in participants receiving ruxolitinib.
Idelalisib 150 mg twice daily in participants receiving ruxolitinib.
Outcomes
Primary Outcome Measures
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure
Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening.
Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Within 28 Days of Idelalisib Exposure
Secondary Outcome Measures
Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure
Percentage of Participants Experiencing Adverse Events Related to Idelalisib Beyond 28 Days of Idelalisib Exposure
Percentage of Participants Experiencing Abnormal Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening.
Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Beyond 28 Days of Exposure
Rate of Overall Response
Rate of overall response as defined by 2013 Revised International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria.
Plasma Concentration of Idelalisib and GS-563117 (Idelalisib Metabolite)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02436135
Brief Title
Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Idelalisib in Adults Receiving Ruxolitinib as Therapy for Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis With Progressive or Relapsed Disease
Acronym
Madison
Official Title
A Phase 1b Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Idelalisib in Subjects Receiving Ruxolitinib as Therapy for Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis With Progressive or Relapsed Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Terminated
Study Start Date
June 5, 2015 (Actual)
Primary Completion Date
November 20, 2017 (Actual)
Study Completion Date
November 20, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of idelalisib in adults receiving ruxolitinib as therapy for intermediate to high-risk primary myelofibrosis (PMF), post-polycythemia vera, or post-essential thrombocythemia myelofibrosis (post-PV MF or post-ET MF) with progressive or relapsed disease.
This is a dose-escalation study. There will be 4 cohorts (A, B, C, D). Participants will receive an escalating dose or dose frequency of idelalisib based on the safety data of available cohort(s).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A, Idelalisib + Ruxolitinib
Arm Type
Experimental
Arm Description
Idelalisib 50 mg once daily in participants receiving ruxolitinib.
Arm Title
Cohort B, Idelalisib + Ruxolitinib
Arm Type
Experimental
Arm Description
Idelalisib 50 mg twice daily in participants receiving ruxolitinib.
Arm Title
Cohort C, Idelalisib + Ruxolitinib
Arm Type
Experimental
Arm Description
Idelalisib 150 mg once daily in participants receiving ruxolitinib.
Arm Title
Cohort D, Idelalisib + Ruxolitinib
Arm Type
Experimental
Arm Description
Idelalisib 150 mg twice daily in participants receiving ruxolitinib.
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
Zydelig®, CAL-101, GS-1101
Intervention Description
Idelalisib tablets administered orally for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Intervention Description
Ruxolitinib will be administered per standard of care according to package insert
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure
Time Frame
First dose date up to 28 days
Title
Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure
Time Frame
First dose date up to 28 days
Title
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
Description
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening.
Time Frame
First dose date up to 28 days
Title
Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Within 28 Days of Idelalisib Exposure
Time Frame
First dose date up to 28 days
Secondary Outcome Measure Information:
Title
Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure
Time Frame
First dose date up to the last dose date (maximum:15.1 months) plus 30 days
Title
Percentage of Participants Experiencing Adverse Events Related to Idelalisib Beyond 28 Days of Idelalisib Exposure
Time Frame
First dose date up to the last dose date (maximum:15.1 months) plus 30 days
Title
Percentage of Participants Experiencing Abnormal Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
Description
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening.
Time Frame
First dose date up to the last dose date (maximum:15.1 months) plus 30 days
Title
Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Beyond 28 Days of Exposure
Time Frame
First dose date up to the last dose date (maximum:15.1 months) plus 30 days
Title
Rate of Overall Response
Description
Rate of overall response as defined by 2013 Revised International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria.
Time Frame
Start of treatment to end of treatment ( up to 15.1 months)
Title
Plasma Concentration of Idelalisib and GS-563117 (Idelalisib Metabolite)
Time Frame
Predose Week 2, 1.5 hour Week 2, and Predose Week 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Individuals must have been on a stable dose of ruxolitinib for at least 4 weeks prior to study entry
Individuals with PMF, post-PV MF, or post-ET MF classified as high risk or intermediate risk as defined by the Dynamic International Prognostic Scoring System (DIPSS) for PMF or DIPSS Plus, if cytogenetics are available
Individuals with PMF, post-PV MF, or post-ET MF who are receiving ruxolitinib and meet 2013 Revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria with progressive and relapsed disease, with modifications for progressive disease complete remission (CR), partial remission (PR), or clinical improvement (CI)
European Cooperative Oncology Group (ECOG) performance status of ≤ 2
Required screening laboratory values as described in the protocol
Willing and able to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions including mandatory prophylaxis for pneumocystis jiroveci pneumonia (PJP)
Able to understand and willing to sign the informed consent form
Key Exclusion Criteria:
Individuals on a stable ruxolitinib dose of 5 mg once daily
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
Ongoing drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver
Ongoing drug-induced pneumonitis
Ongoing inflammatory bowel disease
Ongoing alcohol or drug addiction
Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Known hypersensitivity to the study investigational medicinal product (IMP), the metabolites, or formulation excipients
Unwilling or unable to take oral medication
Unresolved non-hematologic toxicities from prior therapies that are > Common terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of alopecia [Grade 1 or 2 permitted])
Pregnant or lactating females
Cytomegalovirus (CMV): Ongoing infection, treatment, or prophylaxis within the past 28 days
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Idelalisib in Adults Receiving Ruxolitinib as Therapy for Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis With Progressive or Relapsed Disease
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