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

NCT ID: NCT02436135

Last Updated: 2020-09-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-05
• Study Completion Date: 2017-11-20

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).

Conditions

Myelofibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A, Idelalisib + Ruxolitinib

Idelalisib 50 mg once daily in participants receiving ruxolitinib.

Group Type: EXPERIMENTAL

Idelalisib

Intervention Type: DRUG

Idelalisib tablets administered orally for 24 weeks

Ruxolitinib

Intervention Type: DRUG

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

Cohort B, Idelalisib + Ruxolitinib

Idelalisib 50 mg twice daily in participants receiving ruxolitinib.

Group Type: EXPERIMENTAL

Idelalisib

Intervention Type: DRUG

Idelalisib tablets administered orally for 24 weeks

Ruxolitinib

Intervention Type: DRUG

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

Cohort C, Idelalisib + Ruxolitinib

Idelalisib 150 mg once daily in participants receiving ruxolitinib.

Group Type: EXPERIMENTAL

Idelalisib

Intervention Type: DRUG

Idelalisib tablets administered orally for 24 weeks

Ruxolitinib

Intervention Type: DRUG

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

Cohort D, Idelalisib + Ruxolitinib

Idelalisib 150 mg twice daily in participants receiving ruxolitinib.

Group Type: EXPERIMENTAL

Idelalisib

Intervention Type: DRUG

Idelalisib tablets administered orally for 24 weeks

Ruxolitinib

Intervention Type: DRUG

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

Interventions

Idelalisib

Idelalisib tablets administered orally for 24 weeks

Intervention Type: DRUG

Ruxolitinib

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

Intervention Type: DRUG

Other Intervention Names

Zydelig®; CAL-101; GS-1101

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Stanford Hospital and Clinics

Stanford, California, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-397-1245

Identifier Type: -

Identifier Source: org_study_id