MyelofibrosisPhase 1MadisonNCT02436135
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
A Phase 1 study testing Idelalisib and Ruxolitinib in people with Myelofibrosis, run by Gilead Sciences at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis
- What is being tested?
- Idelalisib and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Jun 2015to 20 Nov 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Stanford Hospital and Clinics
Stanford, California, 94305
About this study
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
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).
- Conditions
- Myelofibrosis
- Being tested
- Idelalisib, Ruxolitinib
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdelalisibDrug
Also called Zydelig®, CAL-101, GS-1101
Idelalisib tablets administered orally for 24 weeks
RuxolitinibDrug
Ruxolitinib will be administered per standard of care according to package insert
| Study group | Role | What they receive |
|---|---|---|
| Cohort A, Idelalisib + Ruxolitinib | Experimental | Idelalisib 50 mg once daily in participants receiving ruxolitinib. Receives: Drug: Idelalisib; Drug: Ruxolitinib |
| Cohort B, Idelalisib + Ruxolitinib | Experimental | Idelalisib 50 mg twice daily in participants receiving ruxolitinib. Receives: Drug: Idelalisib; Drug: Ruxolitinib |
| Cohort C, Idelalisib + Ruxolitinib | Experimental | Idelalisib 150 mg once daily in participants receiving ruxolitinib. Receives: Drug: Idelalisib; Drug: Ruxolitinib |
| Cohort D, Idelalisib + Ruxolitinib | Experimental | Idelalisib 150 mg twice daily in participants receiving ruxolitinib. Receives: Drug: Idelalisib; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure
Measured: First dose date up to 28 days
Percentage of Participants Experiencing Adverse Events Related to Idelalisib Within 28 Days of Idelalisib Exposure
Measured: 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.
Measured: 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
Measured: First dose date up to 28 days
Secondary outcomes (6)
Percentage of Participants Experiencing Treatment Emergent Adverse Events Beyond 28 Days of Idelalisib Exposure
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: Start of treatment to end of treatment ( up to 15.1 months)
Plasma Concentration of Idelalisib and GS-563117 (Idelalisib Metabolite)
Measured: Predose Week 2, 1.5 hour Week 2, and Predose Week 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study start5 Jun 2015
- Primary completion20 Nov 2017
- Study completion20 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02436135
- Sponsor's protocol ID
- GS-US-397-1245
- Acronym
- Madison
- Status last verified
- Aug 2020
- First submitted
- 1 May 2015
- Last updated
- 16 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02436135
- Acronym / sponsor ID
- Madison / GS-US-397-1245
- Conditions
- Myelofibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 5 Jun 2015 (actual)
- Primary completion
- 20 Nov 2017 (actual)
- Study completion
- 20 Nov 2017 (actual)
- First posted
- 6 May 2015 (estimated)
- Results
- Posted 14 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A, Idelalisib + Ruxolitinib | Experimental | Drug: Idelalisib, Drug: RuxolitinibIdelalisib 50 mg once daily in participants receiving ruxolitinib. |
| Cohort B, Idelalisib + Ruxolitinib | Experimental | Drug: Idelalisib, Drug: RuxolitinibIdelalisib 50 mg twice daily in participants receiving ruxolitinib. |
| Cohort C, Idelalisib + Ruxolitinib | Experimental | Drug: Idelalisib, Drug: RuxolitinibIdelalisib 150 mg once daily in participants receiving ruxolitinib. |
| Cohort D, Idelalisib + Ruxolitinib | Experimental | Drug: Idelalisib, Drug: RuxolitinibIdelalisib 150 mg twice daily in participants receiving ruxolitinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IdelalisibAlso: Zydelig®, CAL-101, GS-1101Idelalisib tablets administered orally for 24 weeks | Drug | Cohort A, Idelalisib + Ruxolitinib, Cohort B, Idelalisib + Ruxolitinib, Cohort C, Idelalisib + Ruxolitinib, Cohort D, Idelalisib + Ruxolitinib |
| RuxolitinibRuxolitinib will be administered per standard of care according to package insert | Drug | Cohort A, Idelalisib + Ruxolitinib, Cohort B, Idelalisib + Ruxolitinib, Cohort C, Idelalisib + Ruxolitinib, Cohort D, Idelalisib + Ruxolitinib |
Primary outcome
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
Time frame: 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
Time frame: First dose date up to 28 days
6 secondary outcomes
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Idelalisib and Ruxolitinib in people with Myelofibrosis, run by Gilead Sciences at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events Within 28 Days of Idelalisib Exposure (time frame: First dose date up to 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2020.