A Phase 1 interventional study of Idelalisib and Ruxolitinib in Myelofibrosis, sponsored by Gilead Sciences. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-09-16.
Sponsored by Gilead Sciences · Phase 1, Interventional, and Treatment
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).
228 studies on the registry are indexed under Polycythemia Vera; 53 are open to participants now.
This study's enrollment of 10 is below the median of 55 across 174 interventional studies indexed under Polycythemia Vera.
Browse Polycythemia Vera studies →Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.
Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Idelalisib 50 mg once daily in participants receiving ruxolitinib.
Drug: Idelalisib · Drug: Ruxolitinib
Idelalisib 50 mg twice daily in participants receiving ruxolitinib.
Drug: Idelalisib · Drug: Ruxolitinib
Idelalisib 150 mg once daily in participants receiving ruxolitinib.
Drug: Idelalisib · Drug: Ruxolitinib
Idelalisib 150 mg twice daily in participants receiving ruxolitinib.
Drug: Idelalisib · Drug: Ruxolitinib
Idelalisib tablets administered orally for 24 weeks
Also known as: Zydelig®, CAL-101, GS-1101
Ruxolitinib will be administered per standard of care according to package insert
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure
Time frame: First dose date up to 28 days
Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure
Time frame: 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
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
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
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
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
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.
Time frame: First dose date up to the last dose date (maximum:15.1 months) plus 30 days
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
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.
Time frame: Start of treatment to end of treatment ( up to 15.1 months)
Plasma Concentration of Idelalisib and GS-563117 (Idelalisib Metabolite)
Time frame: Predose Week 2, 1.5 hour Week 2, and Predose Week 3
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.
| Milestone | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Started | 6 | 4 |
| Completed | 0 | 0 |
| Not completed | 6 | 4 |
| Withdrew: Progressive disease | 3 | 1 |
| Withdrew: Investigator discretion | 1 | 2 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Withdrawal by participant | 1 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 1 |
| Percentage of participants | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure | 100.0 | 75.0 |
| Percentage of participants | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure | 33.3 | 0 |
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 | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Anemia (Grade 1) | 0 | 0 |
| Anemia (Grade 2) | 0 | 0 |
| Anemia (Grade 3) | 16.7 | 25.0 |
| Anemia (Grade 4) | 0 | 0 |
| White blood cell decreased (Grade 1) | 0 | 0 |
| White blood cell decreased (Grade 2) | 0 | 25.0 |
| White blood cell decreased (Grade 3) | 0 | 0 |
| White blood cell decreased (Grade 4) | 0 | 0 |
| Lymphocyte count decreased (Grade 1) | 0 | 0 |
| Lymphocyte count decreased (Grade 2) | 33.3 | 0 |
| Lymphocyte count decreased (Grade 3) | 16.7 | 25.0 |
| Lymphocyte count decreased (Grade 4) | 0 | 0 |
| Lymphocyte count increased (Grade 1) | 0 | 0 |
| Lymphocyte count increased (Grade 2) | 16.7 | 0 |
| Lymphocyte count increased (Grade 3) | 0 | 0 |
| Lymphocyte count increased (Grade 4) | 0 | 0 |
| Neutrophil count decreased (Grade 1) | 0 | 0 |
| Neutrophil count decreased (Grade 2) | 0 | 25.0 |
| Neutrophil count decreased (Grade 3) | 0 | 0 |
| Neutrophil count decreased (Grade 4) | 0 | 0 |
| Platelet count decreased (Grade 1) | 0 | 25.0 |
| Platelet count decreased (Grade 2) | 0 | 25.0 |
| Platelet count decreased (Grade 3) | 16.7 | 0 |
| Platelet count decreased (Grade 4) | 0 | 0 |
| Alanine aminotransferase increased (Grade 1) | 16.7 | 25.0 |
| Alanine aminotransferase increased (Grade 2) | 0 | 0 |
| Alanine aminotransferase increased (Grade 3) | 0 | 0 |
| Alanine aminotransferase increased (Grade 4) | 0 | 0 |
| Hypocalcemia (Grade 1) | 0 | 25.0 |
| Hypocalcemia (Grade 2) | 0 | 25.0 |
| Hypocalcemia (Grade 3) | 0 | 0 |
| Hypocalcemia (Grade 4) | 0 | 0 |
| Aspartate aminotransferase increased (Grade 1) | 33.3 | 25.0 |
| Aspartate aminotransferase increased (Grade 2) | 0 | 0 |
| Aspartate aminotransferase increased (Grade 3) | 0 | 0 |
| Aspartate aminotransferase increased (Grade 4) | 0 | 0 |
| Blood bilirubin increased (Grade 1) | 16.7 | 0 |
| Blood bilirubin increased (Grade 2) | 0 | 0 |
| Blood bilirubin increased (Grade 3) | 0 | 0 |
| Blood bilirubin increased (Grade 4) | 0 | 0 |
| Creatinine increased (Grade 1) | 16.7 | 50.0 |
| Creatinine increased (Grade 2) | 0 | 0 |
| Creatinine increased (Grade 3) | 0 | 0 |
| Creatinine increased (Grade 4) | 0 | 0 |
| Gamma Glutamyl Transferase Increased (Grade 1) | 16.7 | 0 |
| Gamma Glutamyl Transferase Increased (Grade 2) | 0 | 25.0 |
| Gamma Glutamyl Transferase Increased (Grade 3) | 0 | 0 |
| Gamma Glutamyl Transferase Increased (Grade 4) | 0 | 0 |
| Hypoglycemia (Grade 1) | 16.7 | 0 |
| Hypoglycemia (Grade 2) | 0 | 0 |
| Hypoglycemia (Grade 3) | 0 | 0 |
| Hypoglycemia (Grade 4) | 0 | 0 |
| Hypomagnesemia (Grade 1) | 0 | 25.0 |
| Hypomagnesemia (Grade 2) | 0 | 0 |
| Hypomagnesemia (Grade 3) | 0 | 0 |
| Hypomagnesemia (Grade 4) | 0 | 0 |
| Hyperkalemia (Grade 1) | 0 | 0 |
| Hyperkalemia (Grade 2) | 16.7 | 0 |
| Hyperkalemia (Grade 3) | 0 | 0 |
| Hyperkalemia (Grade 4) | 0 | 0 |
| Hyperuricemia (Grade 1) | 33.3 | 25.0 |
| Hyperuricemia (Grade 2) | 0 | 0 |
| Hyperuricemia (Grade 3) | 0 | 0 |
| Hyperuricemia (Grade 4) | 16.7 | 0 |
| Percentage of participants | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Within 28 Days of Idelalisib Exposure | 0.0 | 0.0 |
| Percentage of participants | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure | 100.0 | 100.0 |
| Percentage of participants | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Percentage of Participants Experiencing Adverse Events Related to Idelalisib Beyond 28 Days of Idelalisib Exposure | 50.0 | 25.0 |
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 | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Anemia (Grade 1) | 0 | 0 |
| Anemia (Grade 2) | 0 | 0 |
| Anemia (Grade 3) | 33.3 | 25.0 |
| Anemia (Grade 4) | 0 | 0 |
| White blood cell decreased (Grade 1) | 16.7 | 0 |
| White blood cell decreased (Grade 2) | 0 | 25.0 |
| White blood cell decreased (Grade 3) | 16.7 | 0 |
| White blood cell decreased (Grade 4) | 0 | 0 |
| Lymphocyte count decreased (Grade 1) | 0 | 0 |
| Lymphocyte count decreased (Grade 2) | 0 | 25.0 |
| Lymphocyte count decreased (Grade 3) | 50.0 | 50.0 |
| Lymphocyte count decreased (Grade 4) | 16.7 | 0 |
| Lymphocyte count increased (Grade 1) | 0 | 0 |
| Lymphocyte count increased (Grade 2) | 33.3 | 25.0 |
| Lymphocyte count increased (Grade 3) | 0 | 0 |
| Lymphocyte count increased (Grade 4) | 0 | 0 |
| Neutrophil count decreased (Grade 1) | 0 | 0 |
| Neutrophil count decreased (Grade 2) | 0 | 0 |
| Neutrophil count decreased (Grade 3) | 16.7 | 25.0 |
| Neutrophil count decreased (Grade 4) | 0 | 0 |
| Platelet count decreased (Grade 1) | 0 | 25.0 |
| Platelet count decreased (Grade 2) | 16.7 | 25.0 |
| Platelet count decreased (Grade 3) | 16.7 | 25.0 |
| Platelet count decreased (Grade 4) | 0 | 25.0 |
| Alanine aminotransferase increased (Grade 1) | 16.7 | 25.0 |
| Alanine aminotransferase increased (Grade 2) | 0 | 25.0 |
| Alanine aminotransferase increased (Grade 3) | 0 | 25.0 |
| Alanine aminotransferase increased (Grade 4) | 0 | 0 |
| Hypocalcemia (Grade 1) | 0 | 25.0 |
| Hypocalcemia (Grade 2) | 0 | 25.0 |
| Hypocalcemia (Grade 3) | 0 | 0 |
| Hypocalcemia (Grade 4) | 0 | 0 |
| Alkaline phosphatase increased (Grade 1) | 16.7 | 0 |
| Alkaline phosphatase increased (Grade 2) | 0 | 0 |
| Alkaline phosphatase increased (Grade 3) | 0 | 0 |
| Alkaline phosphatase increased (Grade 4) | 0 | 0 |
| Aspartate aminotransferase increased (Grade 1) | 50.0 | 50.0 |
| Aspartate aminotransferase increased (Grade 2) | 0 | 25.0 |
| Aspartate aminotransferase increased (Grade 3) | 0 | 0 |
| Aspartate aminotransferase increased (Grade 4) | 0 | 0 |
| Blood bilirubin increased (Grade 1) | 33.3 | 25.0 |
| Blood bilirubin increased (Grade 2) | 0 | 0 |
| Blood bilirubin increased (Grade 3) | 0 | 0 |
| Blood bilirubin increased (Grade 4) | 0 | 0 |
| Creatinine increased (Grade 1) | 16.7 | 50.0 |
| Creatinine increased (Grade 2) | 0 | 0 |
| Creatinine increased (Grade 3) | 0 | 0 |
| Creatinine increased (Grade 4) | 0 | 0 |
| Gamma Glutamyl Transferase Increased (Grade 1) | 50.0 | 25.0 |
| Gamma Glutamyl Transferase Increased (Grade 2) | 0 | 25.0 |
| Gamma Glutamyl Transferase Increased (Grade 3) | 16.7 | 50.0 |
| Gamma Glutamyl Transferase Transferase (Grade 4) | 0 | 0 |
| Hyperglycemia (Grade 1) | 0 | 0 |
| Hyperglycemia (Grade 2) | 0 | 0 |
| Hyperglycemia (Grade 3) | 0 | 25.0 |
| Hyperglycemia (Grade 4) | 0 | 0 |
| Hypoglycemia (Grade 1) | 16.7 | 0 |
| Hypoglycemia (Grade 2) | 0 | 0 |
| Hypoglycemia (Grade 3) | 0 | 0 |
| Hypoglycemia (Grade 4) | 0 | 0 |
| Hypomagnesemia (Grade 1) | 0 | 25.0 |
| Hypomagnesemia (Grade 2) | 0 | 0 |
| Hypomagnesemia (Grade 3) | 0 | 0 |
| Hypomagnesemia (Grade 4) | 0 | 0 |
| Hyperkalemia (Grade 1) | 0 | 25.0 |
| Hyperkalemia (Grade 2) | 16.7 | 0 |
| Hyperkalemia (Grade 3) | 0 | 0 |
| Hyperkalemia (Grade 4) | 0 | 0 |
| Hypokalemia (Grade 1) | 0 | 25.0 |
| Hypokalemia (Grade 2) | 0 | 0 |
| Hypokalemia (Grade 3) | 0 | 0 |
| Hypokalemia (Grade 4) | 0 | 0 |
| Hyponatremia (Grade 1) | 0 | 0 |
| Hyponatremia (Grade 2) | 0 | 0 |
| Hyponatremia (Grade 3) | 0 | 25.0 |
| Hyponatremia (Grade 4) | 0 | 0 |
| Hyperuricemia (Grade 1) | 33.3 | 0 |
| Hyperuricemia (Grade 2) | 0 | 0 |
| Hyperuricemia (Grade 3) | 0 | 0 |
| Hyperuricemia (Grade 4) | 16.7 | 25.0 |
| Percentage of participants | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Percentage of Participants Who Permanently Discontinued Idelalisib Due to an Adverse Event Beyond 28 Days of Exposure | 16.7 | 25.0 |
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.
No measurements were reported for this outcome.
| ng/mL | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| 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 |
Collected over First dose date up to the last dose date (maximum:15.1 months) plus 30 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort A, Idelalisib + Ruxolitinib | 0/6 (0%) | 3/6 (50%) | 6/6 (100%) |
| Cohort B, Idelalisib + Ruxolitinib | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| Event | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 1/6 | 0/4 |
| Abdominal painGastrointestinal disorders | 1/6 | 0/4 |
| NauseaGastrointestinal disorders | 1/6 | 0/4 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/6 | 0/4 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/6 | 0/4 |
| Event | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 2/6 | 2/4 |
| NauseaGastrointestinal disorders | 0/6 | 2/4 |
| FatigueGeneral disorders | 3/6 | 0/4 |
| Urinary tract infectionInfections and infestations | 0/6 | 2/4 |
| MyalgiaMusculoskeletal and connective tissue disorders | 3/6 | 0/4 |
| CoughRespiratory, thoracic and mediastinal disorders | 3/6 | 1/4 |
| Night sweatsSkin and subcutaneous tissue disorders | 1/6 | 2/4 |
| PruritusSkin and subcutaneous tissue disorders | 0/6 | 2/4 |
| *AnaemiaBlood and lymphatic system disorders | 2/6 | 0/4 |
| Abdominal pain upperGastrointestinal disorders | 2/6 | 0/4 |
Full Analysis Set included all participants who took at least 1 dose of study drug.
| Age, Continuous(years) | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | Total |
|---|---|---|---|
| Mean | 62 ± 10.5 | 69 ± 6.1 | 65 ± 9.1 |
| Sex: Female, Male(Participants) | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | Total |
|---|---|---|---|
| Female | 0 | 2 | 2 |
| Male | 6 | 2 | 8 |
| Race/Ethnicity, Customized(Participants) | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | Total |
|---|---|---|---|
| White | 5 | 3 | 8 |
| Others | 1 | 1 | 2 |
| Race/Ethnicity, Customized(Participants) | Cohort A, Idelalisib + Ruxolitinib | Cohort B, Idelalisib + Ruxolitinib | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 6 | 4 | 10 |
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Gilead Sciences