Madison: 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
Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT02436135
Collaborator
(none)
10
2
4
29.5
5
0.2
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
10 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Jun 5, 2015
Actual Primary Completion Date
:
Nov 20, 2017
Actual Study Completion Date
:
Nov 20, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A, Idelalisib + Ruxolitinib Idelalisib 50 mg once daily in participants receiving ruxolitinib. |
Drug: Idelalisib
Idelalisib tablets administered orally for 24 weeks
Other Names:
Drug: Ruxolitinib
Ruxolitinib will be administered per standard of care according to package insert
|
| Experimental: Cohort B, Idelalisib + Ruxolitinib Idelalisib 50 mg twice daily in participants receiving ruxolitinib. |
Drug: Idelalisib
Idelalisib tablets administered orally for 24 weeks
Other Names:
Drug: Ruxolitinib
Ruxolitinib will be administered per standard of care according to package insert
|
| Experimental: Cohort C, Idelalisib + Ruxolitinib Idelalisib 150 mg once daily in participants receiving ruxolitinib. |
Drug: Idelalisib
Idelalisib tablets administered orally for 24 weeks
Other Names:
Drug: Ruxolitinib
Ruxolitinib will be administered per standard of care according to package insert
|
| Experimental: Cohort D, Idelalisib + Ruxolitinib Idelalisib 150 mg twice daily in participants receiving ruxolitinib. |
Drug: Idelalisib
Idelalisib tablets administered orally for 24 weeks
Other Names:
Drug: Ruxolitinib
Ruxolitinib will be administered per standard of care according to package insert
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure [First dose date up to 28 days]
- Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure [First dose date up to 28 days]
- Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline [First dose date up to 28 days]
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 [First dose date up to 28 days]
Secondary Outcome Measures
- Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure [First dose date up to the last dose date (maximum:15.1 months) plus 30 days]
- Percentage of Participants Experiencing Adverse Events Related to Idelalisib Beyond 28 Days of Idelalisib Exposure [First dose date up to the last dose date (maximum:15.1 months) plus 30 days]
- Percentage of Participants Experiencing Abnormal Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline [First dose date up to the last dose date (maximum:15.1 months) plus 30 days]
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 [First dose date up to the last dose date (maximum:15.1 months) plus 30 days]
- Rate of Overall Response [Start of treatment to end of treatment ( up to 15.1 months)]
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) [Predose Week 2, 1.5 hour Week 2, and Predose Week 3]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford Hospital and Clinics | Stanford | California | United States | 94305 |
| 2 | University of Michigan Health System | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02436135
Other Study ID Numbers:
- GS-US-397-1245
First Posted:
May 6, 2015
Last Update Posted:
Sep 16, 2020
Last Verified:
Aug 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in the United States. The first participant was screened on 05 June 2015. The last study visit occurred on 20 November 2017. |
|---|---|
| Pre-assignment Detail | 12 participants were screened. Participants were enrolled in Cohorts A and B. After the fourth participant in Cohort B was enrolled, the study was terminated. No additional participants were enrolled. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for primary myelofibrosis (PMF), post- polycythemia vera (PV) myelofibrosis (MF), or post-essential thrombocythemia (ET) MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Period Title: Overall Study | ||
| STARTED | 6 | 4 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 6 | 4 |
Baseline Characteristics
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | Total |
|---|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. | Total of all reporting groups |
| Overall Participants | 6 | 4 | 10 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
62
(10.5)
|
69
(6.1)
|
65
(9.1)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
2
50%
|
2
20%
|
| Male |
6
100%
|
2
50%
|
8
80%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
5
83.3%
|
3
75%
|
8
80%
|
| Others |
1
16.7%
|
1
25%
|
2
20%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
6
100%
|
4
100%
|
10
100%
|
Outcome Measures
| Title | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure |
|---|---|
| Description | |
| Time Frame | First dose date up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set included all participants who took at least 1 dose of study drug. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Number [Percentage of participants] |
100.0
1666.7%
|
75.0
1875%
|
| Title | Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure |
|---|---|
| Description | |
| Time Frame | First dose date up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Number [Percentage of participants] |
33.3
555%
|
0
0%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Anemia (Grade 1) |
0
0%
|
0
0%
|
| Anemia (Grade 2) |
0
0%
|
0
0%
|
| Anemia (Grade 3) |
16.7
278.3%
|
25.0
625%
|
| Anemia (Grade 4) |
0
0%
|
0
0%
|
| White blood cell decreased (Grade 1) |
0
0%
|
0
0%
|
| White blood cell decreased (Grade 2) |
0
0%
|
25.0
625%
|
| White blood cell decreased (Grade 3) |
0
0%
|
0
0%
|
| White blood cell decreased (Grade 4) |
0
0%
|
0
0%
|
| Lymphocyte count decreased (Grade 1) |
0
0%
|
0
0%
|
| Lymphocyte count decreased (Grade 2) |
33.3
555%
|
0
0%
|
| Lymphocyte count decreased (Grade 3) |
16.7
278.3%
|
25.0
625%
|
| Lymphocyte count decreased (Grade 4) |
0
0%
|
0
0%
|
| Lymphocyte count increased (Grade 1) |
0
0%
|
0
0%
|
| Lymphocyte count increased (Grade 2) |
16.7
278.3%
|
0
0%
|
| Lymphocyte count increased (Grade 3) |
0
0%
|
0
0%
|
| Lymphocyte count increased (Grade 4) |
0
0%
|
0
0%
|
| Neutrophil count decreased (Grade 1) |
0
0%
|
0
0%
|
| Neutrophil count decreased (Grade 2) |
0
0%
|
25.0
625%
|
| Neutrophil count decreased (Grade 3) |
0
0%
|
0
0%
|
| Neutrophil count decreased (Grade 4) |
0
0%
|
0
0%
|
| Platelet count decreased (Grade 1) |
0
0%
|
25.0
625%
|
| Platelet count decreased (Grade 2) |
0
0%
|
25.0
625%
|
| Platelet count decreased (Grade 3) |
16.7
278.3%
|
0
0%
|
| Platelet count decreased (Grade 4) |
0
0%
|
0
0%
|
| Alanine aminotransferase increased (Grade 1) |
16.7
278.3%
|
25.0
625%
|
| Alanine aminotransferase increased (Grade 2) |
0
0%
|
0
0%
|
| Alanine aminotransferase increased (Grade 3) |
0
0%
|
0
0%
|
| Alanine aminotransferase increased (Grade 4) |
0
0%
|
0
0%
|
| Hypocalcemia (Grade 1) |
0
0%
|
25.0
625%
|
| Hypocalcemia (Grade 2) |
0
0%
|
25.0
625%
|
| Hypocalcemia (Grade 3) |
0
0%
|
0
0%
|
| Hypocalcemia (Grade 4) |
0
0%
|
0
0%
|
| Aspartate aminotransferase increased (Grade 1) |
33.3
555%
|
25.0
625%
|
| Aspartate aminotransferase increased (Grade 2) |
0
0%
|
0
0%
|
| Aspartate aminotransferase increased (Grade 3) |
0
0%
|
0
0%
|
| Aspartate aminotransferase increased (Grade 4) |
0
0%
|
0
0%
|
| Blood bilirubin increased (Grade 1) |
16.7
278.3%
|
0
0%
|
| Blood bilirubin increased (Grade 2) |
0
0%
|
0
0%
|
| Blood bilirubin increased (Grade 3) |
0
0%
|
0
0%
|
| Blood bilirubin increased (Grade 4) |
0
0%
|
0
0%
|
| Creatinine increased (Grade 1) |
16.7
278.3%
|
50.0
1250%
|
| Creatinine increased (Grade 2) |
0
0%
|
0
0%
|
| Creatinine increased (Grade 3) |
0
0%
|
0
0%
|
| Creatinine increased (Grade 4) |
0
0%
|
0
0%
|
| Gamma Glutamyl Transferase Increased (Grade 1) |
16.7
278.3%
|
0
0%
|
| Gamma Glutamyl Transferase Increased (Grade 2) |
0
0%
|
25.0
625%
|
| Gamma Glutamyl Transferase Increased (Grade 3) |
0
0%
|
0
0%
|
| Gamma Glutamyl Transferase Increased (Grade 4) |
0
0%
|
0
0%
|
| Hypoglycemia (Grade 1) |
16.7
278.3%
|
0
0%
|
| Hypoglycemia (Grade 2) |
0
0%
|
0
0%
|
| Hypoglycemia (Grade 3) |
0
0%
|
0
0%
|
| Hypoglycemia (Grade 4) |
0
0%
|
0
0%
|
| Hypomagnesemia (Grade 1) |
0
0%
|
25.0
625%
|
| Hypomagnesemia (Grade 2) |
0
0%
|
0
0%
|
| Hypomagnesemia (Grade 3) |
0
0%
|
0
0%
|
| Hypomagnesemia (Grade 4) |
0
0%
|
0
0%
|
| Hyperkalemia (Grade 1) |
0
0%
|
0
0%
|
| Hyperkalemia (Grade 2) |
16.7
278.3%
|
0
0%
|
| Hyperkalemia (Grade 3) |
0
0%
|
0
0%
|
| Hyperkalemia (Grade 4) |
0
0%
|
0
0%
|
| Hyperuricemia (Grade 1) |
33.3
555%
|
25.0
625%
|
| Hyperuricemia (Grade 2) |
0
0%
|
0
0%
|
| Hyperuricemia (Grade 3) |
0
0%
|
0
0%
|
| Hyperuricemia (Grade 4) |
16.7
278.3%
|
0
0%
|
| Title | Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Within 28 Days of Idelalisib Exposure |
|---|---|
| Description | |
| Time Frame | First dose date up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Number [Percentage of participants] |
0.0
0%
|
0.0
0%
|
| Title | Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure |
|---|---|
| Description | |
| Time Frame | First dose date up to the last dose date (maximum:15.1 months) plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Number [Percentage of participants] |
100.0
1666.7%
|
100.0
2500%
|
| Title | Percentage of Participants Experiencing Adverse Events Related to Idelalisib Beyond 28 Days of Idelalisib Exposure |
|---|---|
| Description | |
| Time Frame | First dose date up to the last dose date (maximum:15.1 months) plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Number [Percentage of participants] |
50.0
833.3%
|
25.0
625%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Anemia (Grade 1) |
0
0%
|
0
0%
|
| Anemia (Grade 2) |
0
0%
|
0
0%
|
| Anemia (Grade 3) |
33.3
555%
|
25.0
625%
|
| Anemia (Grade 4) |
0
0%
|
0
0%
|
| White blood cell decreased (Grade 1) |
16.7
278.3%
|
0
0%
|
| White blood cell decreased (Grade 2) |
0
0%
|
25.0
625%
|
| White blood cell decreased (Grade 3) |
16.7
278.3%
|
0
0%
|
| White blood cell decreased (Grade 4) |
0
0%
|
0
0%
|
| Lymphocyte count decreased (Grade 1) |
0
0%
|
0
0%
|
| Lymphocyte count decreased (Grade 2) |
0
0%
|
25.0
625%
|
| Lymphocyte count decreased (Grade 3) |
50.0
833.3%
|
50.0
1250%
|
| Lymphocyte count decreased (Grade 4) |
16.7
278.3%
|
0
0%
|
| Lymphocyte count increased (Grade 1) |
0
0%
|
0
0%
|
| Lymphocyte count increased (Grade 2) |
33.3
555%
|
25.0
625%
|
| Lymphocyte count increased (Grade 3) |
0
0%
|
0
0%
|
| Lymphocyte count increased (Grade 4) |
0
0%
|
0
0%
|
| Neutrophil count decreased (Grade 1) |
0
0%
|
0
0%
|
| Neutrophil count decreased (Grade 2) |
0
0%
|
0
0%
|
| Neutrophil count decreased (Grade 3) |
16.7
278.3%
|
25.0
625%
|
| Neutrophil count decreased (Grade 4) |
0
0%
|
0
0%
|
| Platelet count decreased (Grade 1) |
0
0%
|
25.0
625%
|
| Platelet count decreased (Grade 2) |
16.7
278.3%
|
25.0
625%
|
| Platelet count decreased (Grade 3) |
16.7
278.3%
|
25.0
625%
|
| Platelet count decreased (Grade 4) |
0
0%
|
25.0
625%
|
| Alanine aminotransferase increased (Grade 1) |
16.7
278.3%
|
25.0
625%
|
| Alanine aminotransferase increased (Grade 2) |
0
0%
|
25.0
625%
|
| Alanine aminotransferase increased (Grade 3) |
0
0%
|
25.0
625%
|
| Alanine aminotransferase increased (Grade 4) |
0
0%
|
0
0%
|
| Hypocalcemia (Grade 1) |
0
0%
|
25.0
625%
|
| Hypocalcemia (Grade 2) |
0
0%
|
25.0
625%
|
| Hypocalcemia (Grade 3) |
0
0%
|
0
0%
|
| Hypocalcemia (Grade 4) |
0
0%
|
0
0%
|
| Alkaline phosphatase increased (Grade 1) |
16.7
278.3%
|
0
0%
|
| Alkaline phosphatase increased (Grade 2) |
0
0%
|
0
0%
|
| Alkaline phosphatase increased (Grade 3) |
0
0%
|
0
0%
|
| Alkaline phosphatase increased (Grade 4) |
0
0%
|
0
0%
|
| Aspartate aminotransferase increased (Grade 1) |
50.0
833.3%
|
50.0
1250%
|
| Aspartate aminotransferase increased (Grade 2) |
0
0%
|
25.0
625%
|
| Aspartate aminotransferase increased (Grade 3) |
0
0%
|
0
0%
|
| Aspartate aminotransferase increased (Grade 4) |
0
0%
|
0
0%
|
| Blood bilirubin increased (Grade 1) |
33.3
555%
|
25.0
625%
|
| Blood bilirubin increased (Grade 2) |
0
0%
|
0
0%
|
| Blood bilirubin increased (Grade 3) |
0
0%
|
0
0%
|
| Blood bilirubin increased (Grade 4) |
0
0%
|
0
0%
|
| Creatinine increased (Grade 1) |
16.7
278.3%
|
50.0
1250%
|
| Creatinine increased (Grade 2) |
0
0%
|
0
0%
|
| Creatinine increased (Grade 3) |
0
0%
|
0
0%
|
| Creatinine increased (Grade 4) |
0
0%
|
0
0%
|
| Gamma Glutamyl Transferase Increased (Grade 1) |
50.0
833.3%
|
25.0
625%
|
| Gamma Glutamyl Transferase Increased (Grade 2) |
0
0%
|
25.0
625%
|
| Gamma Glutamyl Transferase Increased (Grade 3) |
16.7
278.3%
|
50.0
1250%
|
| Gamma Glutamyl Transferase Transferase (Grade 4) |
0
0%
|
0
0%
|
| Hyperglycemia (Grade 1) |
0
0%
|
0
0%
|
| Hyperglycemia (Grade 2) |
0
0%
|
0
0%
|
| Hyperglycemia (Grade 3) |
0
0%
|
25.0
625%
|
| Hyperglycemia (Grade 4) |
0
0%
|
0
0%
|
| Hypoglycemia (Grade 1) |
16.7
278.3%
|
0
0%
|
| Hypoglycemia (Grade 2) |
0
0%
|
0
0%
|
| Hypoglycemia (Grade 3) |
0
0%
|
0
0%
|
| Hypoglycemia (Grade 4) |
0
0%
|
0
0%
|
| Hypomagnesemia (Grade 1) |
0
0%
|
25.0
625%
|
| Hypomagnesemia (Grade 2) |
0
0%
|
0
0%
|
| Hypomagnesemia (Grade 3) |
0
0%
|
0
0%
|
| Hypomagnesemia (Grade 4) |
0
0%
|
0
0%
|
| Hyperkalemia (Grade 1) |
0
0%
|
25.0
625%
|
| Hyperkalemia (Grade 2) |
16.7
278.3%
|
0
0%
|
| Hyperkalemia (Grade 3) |
0
0%
|
0
0%
|
| Hyperkalemia (Grade 4) |
0
0%
|
0
0%
|
| Hypokalemia (Grade 1) |
0
0%
|
25.0
625%
|
| Hypokalemia (Grade 2) |
0
0%
|
0
0%
|
| Hypokalemia (Grade 3) |
0
0%
|
0
0%
|
| Hypokalemia (Grade 4) |
0
0%
|
0
0%
|
| Hyponatremia (Grade 1) |
0
0%
|
0
0%
|
| Hyponatremia (Grade 2) |
0
0%
|
0
0%
|
| Hyponatremia (Grade 3) |
0
0%
|
25.0
625%
|
| Hyponatremia (Grade 4) |
0
0%
|
0
0%
|
| Hyperuricemia (Grade 1) |
33.3
555%
|
0
0%
|
| Hyperuricemia (Grade 2) |
0
0%
|
0
0%
|
| Hyperuricemia (Grade 3) |
0
0%
|
0
0%
|
| Hyperuricemia (Grade 4) |
16.7
278.3%
|
25.0
625%
|
| Title | Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Beyond 28 Days of Exposure |
|---|---|
| Description | |
| Time Frame | First dose date up to the last dose date (maximum:15.1 months) plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Number [Percentage of participants] |
16.7
278.3%
|
25.0
625%
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was prematurely terminated due to safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 0 | 0 |
| Title | Plasma Concentration of Idelalisib and GS-563117 (Idelalisib Metabolite) |
|---|---|
| Description | |
| Time Frame | Predose Week 2, 1.5 hour Week 2, and Predose Week 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) Analysis Set included all enrolled participants who took at least 1 dose of study drug and have at least 1 nonmissing postdose value reported by the PK laboratory. |
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. |
| Measure Participants | 6 | 4 |
| Idelalisib: Predose Week 2 |
9.95
(6.534)
|
106.83
(107.549)
|
| Idelalisib: 1.5 hour Postdose Week 2 |
835.00
(487.102)
|
760.25
(438.644)
|
| Idelalisib: Predose Week 3 |
6.67
(1.770)
|
90.25
(85.374)
|
| GS-563117: Predose Week 2 |
396.6
(406.95)
|
1156.8
(1252.69)
|
| GS-563117: 1.5 hour Postdose Week 2 |
1051.4
(692.36)
|
1405.5
(1228.45)
|
| GS-563117: Predose Week 3 |
227.9
(212.10)
|
988.0
(1018.05)
|
Adverse Events
| Time Frame | First dose date up to the last dose date (maximum:15.1 months) plus 30 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Full Analysis Set included all participants who took at least 1 dose of study drug. | |||
| Arm/Group Title | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | ||
| Arm/Group Description | Idelalisib tablet 50 mg orally once daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post- PV myelofibrosis, or post-ET MF. | Idelalisib tablet 50 mg orally twice daily for 24 weeks in participants receiving ruxolitinib as therapy for PMF, post-PV myelofibrosis or post-ET MF. | ||
All Cause Mortality |
||||
| Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/4 (0%) | ||
Serious Adverse Events |
||||
| Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 0/4 (0%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 1/6 (16.7%) | 0/4 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/6 (16.7%) | 0/4 (0%) | ||
| Nausea | 1/6 (16.7%) | 0/4 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/6 (16.7%) | 0/4 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 1/6 (16.7%) | 0/4 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 4/4 (100%) | ||
| Blood and lymphatic system disorders | ||||
| *Anaemia | 2/6 (33.3%) | 0/4 (0%) | ||
| Eosinophilia | 1/6 (16.7%) | 0/4 (0%) | ||
| Leukocytosis | 0/6 (0%) | 1/4 (25%) | ||
| Leukopenia | 0/6 (0%) | 1/4 (25%) | ||
| Neutropenia | 0/6 (0%) | 1/4 (25%) | ||
| Thrombocytopenia | 0/6 (0%) | 1/4 (25%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 0/6 (0%) | 1/4 (25%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/6 (16.7%) | 1/4 (25%) | ||
| Abdominal distension | 1/6 (16.7%) | 0/4 (0%) | ||
| Abdominal pain | 1/6 (16.7%) | 0/4 (0%) | ||
| Abdominal pain lower | 1/6 (16.7%) | 0/4 (0%) | ||
| Abdominal pain upper | 2/6 (33.3%) | 0/4 (0%) | ||
| Aphthous ulcer | 0/6 (0%) | 1/4 (25%) | ||
| Constipation | 0/6 (0%) | 1/4 (25%) | ||
| Diarrhoea | 2/6 (33.3%) | 2/4 (50%) | ||
| Eructation | 1/6 (16.7%) | 0/4 (0%) | ||
| Hypoaesthesia oral | 1/6 (16.7%) | 0/4 (0%) | ||
| Nausea | 0/6 (0%) | 2/4 (50%) | ||
| Oral pain | 0/6 (0%) | 1/4 (25%) | ||
| Rectal haemorrhage | 1/6 (16.7%) | 0/4 (0%) | ||
| Stomatitis | 0/6 (0%) | 1/4 (25%) | ||
| Vomiting | 0/6 (0%) | 1/4 (25%) | ||
| General disorders | ||||
| Chest pain | 1/6 (16.7%) | 0/4 (0%) | ||
| Chills | 2/6 (33.3%) | 0/4 (0%) | ||
| Fatigue | 3/6 (50%) | 0/4 (0%) | ||
| Influenza like illness | 0/6 (0%) | 1/4 (25%) | ||
| Oedema peripheral | 1/6 (16.7%) | 0/4 (0%) | ||
| Pyrexia | 1/6 (16.7%) | 0/4 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 1/6 (16.7%) | 1/4 (25%) | ||
| Infections and infestations | ||||
| Bronchitis | 1/6 (16.7%) | 0/4 (0%) | ||
| Herpes simplex | 1/6 (16.7%) | 0/4 (0%) | ||
| Nasopharyngitis | 0/6 (0%) | 1/4 (25%) | ||
| Oral herpes | 1/6 (16.7%) | 1/4 (25%) | ||
| Pneumonia | 0/6 (0%) | 1/4 (25%) | ||
| Respiratory syncytial virus infection | 0/6 (0%) | 1/4 (25%) | ||
| Upper respiratory tract infection | 0/6 (0%) | 1/4 (25%) | ||
| Urinary tract infection | 0/6 (0%) | 2/4 (50%) | ||
| Injury, poisoning and procedural complications | ||||
| Allergic transfusion reaction | 0/6 (0%) | 1/4 (25%) | ||
| Contusion | 0/6 (0%) | 1/4 (25%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 0/6 (0%) | 1/4 (25%) | ||
| Aspartate aminotransferase increased | 0/6 (0%) | 1/4 (25%) | ||
| Blood creatinine increased | 1/6 (16.7%) | 0/4 (0%) | ||
| Blood phosphorus decreased | 1/6 (16.7%) | 0/4 (0%) | ||
| Gamma-glutamyltransferase increased | 1/6 (16.7%) | 0/4 (0%) | ||
| Lipase increased | 1/6 (16.7%) | 0/4 (0%) | ||
| Liver function test increased | 0/6 (0%) | 1/4 (25%) | ||
| Serum ferritin increased | 0/6 (0%) | 1/4 (25%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperkalaemia | 1/6 (16.7%) | 0/4 (0%) | ||
| Hypocalcaemia | 0/6 (0%) | 1/4 (25%) | ||
| Iron deficiency | 1/6 (16.7%) | 0/4 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/6 (16.7%) | 0/4 (0%) | ||
| Back pain | 1/6 (16.7%) | 0/4 (0%) | ||
| Muscle spasms | 2/6 (33.3%) | 1/4 (25%) | ||
| Musculoskeletal pain | 1/6 (16.7%) | 0/4 (0%) | ||
| Myalgia | 3/6 (50%) | 0/4 (0%) | ||
| Pain in extremity | 0/6 (0%) | 1/4 (25%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute myeloid leukaemia | 0/6 (0%) | 1/4 (25%) | ||
| Basal cell carcinoma | 0/6 (0%) | 1/4 (25%) | ||
| Skin papilloma | 0/6 (0%) | 1/4 (25%) | ||
| Squamous cell carcinoma of skin | 0/6 (0%) | 1/4 (25%) | ||
| Nervous system disorders | ||||
| Dysaesthesia | 1/6 (16.7%) | 0/4 (0%) | ||
| Headache | 0/6 (0%) | 1/4 (25%) | ||
| Hypoaesthesia | 1/6 (16.7%) | 0/4 (0%) | ||
| Tremor | 1/6 (16.7%) | 0/4 (0%) | ||
| Psychiatric disorders | ||||
| Insomnia | 1/6 (16.7%) | 1/4 (25%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/6 (0%) | 1/4 (25%) | ||
| Haematuria | 1/6 (16.7%) | 0/4 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 3/6 (50%) | 1/4 (25%) | ||
| Dyspnoea | 2/6 (33.3%) | 0/4 (0%) | ||
| Dyspnoea exertional | 0/6 (0%) | 1/4 (25%) | ||
| Epistaxis | 1/6 (16.7%) | 0/4 (0%) | ||
| Lower respiratory tract congestion | 1/6 (16.7%) | 0/4 (0%) | ||
| Oropharyngeal pain | 1/6 (16.7%) | 0/4 (0%) | ||
| Rhinorrhoea | 1/6 (16.7%) | 1/4 (25%) | ||
| Throat irritation | 1/6 (16.7%) | 0/4 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Night sweats | 1/6 (16.7%) | 2/4 (50%) | ||
| Pruritus | 0/6 (0%) | 2/4 (50%) | ||
| Rash generalised | 0/6 (0%) | 1/4 (25%) | ||
| Rash papular | 1/6 (16.7%) | 0/4 (0%) | ||
| Rosacea | 1/6 (16.7%) | 0/4 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02436135
Other Study ID Numbers:
- GS-US-397-1245
First Posted:
May 6, 2015
Last Update Posted:
Sep 16, 2020
Last Verified:
Aug 1, 2020