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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)

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ClinicalTrials.gov Identifier: NCT02436135
Recruitment Status : Completed
First Posted : May 6, 2015
Last Update Posted : December 4, 2017
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy 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.

Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: Idelalisib Drug: Ruxolitinib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group 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 : June 5, 2015
Actual Primary Completion Date : November 20, 2017
Actual Study Completion Date : November 20, 2017


Arm Intervention/treatment
Experimental: Idelalisib Dose Escalation
Four successive cohorts of participants will each be started on a fixed dose of idelalisib. Based on safety data after the third participant completes Day 28, the cohort may be expanded to enroll an additional 3 participants. After the sixth participant completes Day 56, the next cohort will be open to enrollment after safety and PK data at this dose have been evaluated. For the successive 3 cohorts, enrollment will be expanded based on cumulative safety and PK data. Participants will continue ruxolitinib dosing during screening and throughout the study treatment period.
Drug: Idelalisib
Idelalisib tablets administered orally for 24 weeks
Other Names:
  • Zydelig®
  • CAL-101
  • GS-1101

Drug: Ruxolitinib
Ruxolitinib will be administered per standard of care according to package insert




Primary Outcome Measures :
  1. Adverse events (AEs), abnormal laboratory tests, and drug discontinuations due to AEs and serious AEs [ Time Frame: Up to 28 days ]
    This endpoint will measure the safety profile of idelalisib and ruxolitinib after 28 days of exposure.

  2. Plasma pharmacokinetics (PK) profiles of ruxolitinib (and metabolite[s], as applicable) and idelalisib and/or its primary metabolite, GS-563117: Cmax, Tmax, AUC, and Ctrough [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 10; predose and 1.5 hour postdose on Days 15, 36, 78 and 162 ]
    This endpoint will measure the plasma PK profiles of ruxolitinib (and metabolite[s], as applicable) and idelalisib and/or its primary metabolite, GS-563117. PK parameters that will be measured include Cmax, Tmax, AUC, and Ctrough.


Secondary Outcome Measures :
  1. AEs, abnormal laboratory tests, and drug discontinuations due to AEs and serious AEs [ Time Frame: Up to 24 weeks plus 30 days ]
    This endpoint will measure the safety profile of idelalisib and ruxolitinib beyond 28 days of exposure.

  2. Rate of overall response [ Time Frame: Up to 24 weeks ]
    Overall response will be measured by complete response, partial response, or clinical improvement.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02436135


Locations
United States, California
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02436135     History of Changes
Other Study ID Numbers: GS-US-397-1245
First Posted: May 6, 2015    Key Record Dates
Last Update Posted: December 4, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Idelalisib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action