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

NCT02436135 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: GS-US-397-1245
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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

  First dose date up to 28 days

Secondary Outcomes (6)

• 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

• 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)

Study Arms (4)

Cohort A, Idelalisib + Ruxolitinib

EXPERIMENTAL

Idelalisib 50 mg once daily in participants receiving ruxolitinib.

Drug: Idelalisib; Drug: Ruxolitinib

Cohort B, Idelalisib + Ruxolitinib

EXPERIMENTAL

Idelalisib 50 mg twice daily in participants receiving ruxolitinib.

Drug: Idelalisib; Drug: Ruxolitinib

Cohort C, Idelalisib + Ruxolitinib

EXPERIMENTAL

Idelalisib 150 mg once daily in participants receiving ruxolitinib.

Drug: Idelalisib; Drug: Ruxolitinib

Cohort D, Idelalisib + Ruxolitinib

EXPERIMENTAL

Idelalisib 150 mg twice daily in participants receiving ruxolitinib.

Drug: Idelalisib; Drug: Ruxolitinib

Interventions

Idelalisib DRUG

Idelalisib tablets administered orally for 24 weeks

Also known as: Zydelig®, CAL-101, GS-1101

Cohort A, Idelalisib + Ruxolitinib; Cohort B, Idelalisib + Ruxolitinib; Cohort C, Idelalisib + Ruxolitinib; Cohort D, Idelalisib + Ruxolitinib

Ruxolitinib DRUG

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

Cohort A, Idelalisib + Ruxolitinib; Cohort B, Idelalisib + Ruxolitinib; Cohort C, Idelalisib + Ruxolitinib; Cohort D, Idelalisib + Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (2)

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

idelalisib; ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2015
• First Posted: May 6, 2015
• Study Start: June 5, 2015
• Primary Completion: November 20, 2017
• Study Completion: November 20, 2017
• Last Updated: September 16, 2020
• Results First Posted: August 14, 2020

Record last verified: 2020-08

Locations

US (2)