Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies

May 18, 2020 updated by: Gilead Sciences

A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Combination With Idelalisib in Subjects With Relapsed or Refractory Hematologic Malignancies

This study will evaluate the efficacy of the combination entospletinib and idelalisib in participants with relapsed or refractory hematologic malignancies. Participants will be enrolled who have one of the following hematological tumor types: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or indolent non-Hodgkin lymphomas (iNHL; including follicular lymphoma (FL) and lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia [LPL/WM], small lymphocytic lymphoma [SLL], or marginal zone lymphoma [MZL]).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Long Beach, California, United States, 90813
        • Pacific Shores Medical Group
      • Oxnard, California, United States, 93030
        • Ventura County Hematology Oncology Specialists
      • Santa Barbara, California, United States, 93105
        • Cancer Center of Santa Barbara
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Boynton Beach, Florida, United States, 33435
        • Collaborative Research Group LLC
    • New York
      • New York, New York, United States, 10021
        • Weill Cornell Medical College
      • Rochester, New York, United States, 14642
        • University of Rochester, James P. Wilmot Cancer Center
    • Ohio
      • Middletown, Ohio, United States, 45042
        • Signal Point Clinical Research Center, LLC
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • South Carolina
      • Charleston, South Carolina, United States, 29414
        • Charleston Hematology Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Tacoma, Washington, United States, 98405
        • Northwest Medical Specialties

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Diagnosis of B-cell indolent non-Hodgkin lymphoma (iNHL),diffuse large B-cell lymphoma (DLBCL),mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) as documented by medical records and with histology based on criteria established by the World Health Organization
  • For institutions that have Phase 3 or Phase 4 protocols studying idelalisib (Zydelig®; GS-1101); individuals with malignancies being studied in these protocols must have failed screening and be registered as a screen failure in the respective idelalisib protocol
  • Prior treatment for lymphoid malignancy
  • Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
  • Discontinuation of all therapy for the treatment of cancer ≥ 3 weeks before the start of study drug
  • All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study drug
  • Karnofsky performance status of ≥ 60
  • Life expectancy of at least 3 months

Key Exclusion Criteria:

  • Known histological transformation from iNHL or CLL to an aggressive form of NHL (ie, Richter transformation)
  • Known active central nervous system or leptomeningeal lymphoma
  • Presence of known intermediate- or high-grade myelodysplastic syndrome
  • Current therapy with agents that reduce gastric acidity, including but not limited to antacids, H2 inhibitors, and proton pump inhibitors
  • Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study drug
  • Ongoing liver injury
  • Ongoing or recent hepatic encephalopathy
  • Ongoing drug-induced pneumonitis
  • Ongoing inflammatory bowel disease
  • Ongoing alcohol or drug addiction
  • Pregnancy or breastfeeding
  • History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
  • Ongoing immunosuppressive therapy
  • Concurrent participation in an investigational drug trial with therapeutic intent

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Entospletinib + idelalisib

Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg).

After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy.
Drug: Entospletinib
Entospletinib tablets administered orally twice daily
Other Names:
  • GS-9973
Drug: Idelalisib
Idelalisib tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • GS 1101
  • Cal-101
  • Cal 101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Start of treatment to end of treatment (Up to 18 months)
ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response [VGPR] or minor response [MR] for participants with LPL/WM). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively.
Start of treatment to end of treatment (Up to 18 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame: First dose date up to the last dose date plus 30 days (maximum duration: 19 months)
A treatment-emergent Adverse Event (AE) was defined as any AE with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drugs or an AE leading to premature discontinuation of study drug. An AE is any untoward medical occurrence in a clinical investigation where participants administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.
First dose date up to the last dose date plus 30 days (maximum duration: 19 months)
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Time Frame: First dose date up to the last dose date plus 30 days (maximum: 18 months)
A treatment-emergent laboratory (Hematology, Serum Chemistry and Urinalysis) abnormality was defined as an abnormality that, compared to baseline, worsens by ≥ 1 grade in the period from the first dose of study drug. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening or disabling. If baseline data are missing, then any graded abnormality (i.e., an abnormality that is Grade ≥ 1 in severity) will be considered treatment-emergent. The percentage of participants in each worst postbaseline grade is reported.
First dose date up to the last dose date plus 30 days (maximum: 18 months)
Maximum Tolerated Dose Level
Time Frame: First dose (entospelinib + idelalisib) date up to 6 months
Maximum tolerated dose (MTD) is defined as the highest dose level that was consistently well tolerated without dose limiting toxicity (DLT) for the majority of participants time on treatment (ie,> 50%) as determined by the investigator for each participant. DLTs are defined as Grade 4 hematological toxicities persisting for ≥ 14 days or Grade ≥ 3 toxicities of other types.
First dose (entospelinib + idelalisib) date up to 6 months
Progression-free Survival (PFS)
Time Frame: Start of treatment to end of treatment (Up to 18 months)
PFS was defined as the interval from the first dose of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.
Start of treatment to end of treatment (Up to 18 months)
Duration of Response (DOR)
Time Frame: Start of treatment to end of treatment (Up to 18 months)
DOR was defined as the interval from the first-time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.
Start of treatment to end of treatment (Up to 18 months)
Time to Response (TTR)
Time Frame: Start of treatment to end of treatment (Up to 18 months)
TTR was defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is first achieved. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.
Start of treatment to end of treatment (Up to 18 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2013

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

December 22, 2016

Study Registration Dates

First Submitted

February 19, 2013

First Submitted That Met QC Criteria

February 19, 2013

First Posted (Estimate)

February 21, 2013

Study Record Updates

Last Update Posted (Actual)

June 2, 2020

Last Update Submitted That Met QC Criteria

May 18, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-339-0103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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