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

NCT01796470 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: GS-US-339-0103
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 13

Brief Summary

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 \[MZL\]).

Conditions

Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Diffuse Large B-cell Lymphoma; Indolent Non-Hodgkin's Lymphoma

Keywords

GS-US-339-0103; SYK inhibitor; PI3K inhibitor; GS-9973; GS 9973; GS-1101; GS 1101; Cal-101; Cal 101; idelalisib; leukemia; lymphoma; CLL; MCL; DLBCL; iNHL; FL; MZL; LPL; SLL; WM; Waldenström's macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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 Outcomes (6)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events

  First dose date up to the last dose date plus 30 days (maximum duration: 19 months)

• Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

  First dose date up to the last dose date plus 30 days (maximum: 18 months)

• Maximum Tolerated Dose Level

  First dose (entospelinib + idelalisib) date up to 6 months

• Progression-free Survival (PFS)

  Start of treatment to end of treatment (Up to 18 months)

• Duration of Response (DOR)

  Start of treatment to end of treatment (Up to 18 months)

Study Arms (1)

Entospletinib + idelalisib

EXPERIMENTAL

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; Drug: Idelalisib

Interventions

Entospletinib DRUG

Entospletinib tablets administered orally twice daily

Also known as: GS-9973

Entospletinib + idelalisib

Idelalisib DRUG

Idelalisib tablets administered orally twice daily

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

Entospletinib + idelalisib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (13)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Ventura County Hematology Oncology Specialists

Oxnard, California, 93030, United States

Location

Cancer Center of Santa Barbara

Santa Barbara, California, 93105, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Collaborative Research Group LLC

Boynton Beach, Florida, 33435, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

University of Rochester, James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

Location

Signal Point Clinical Research Center, LLC

Middletown, Ohio, 45042, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Charleston Hematology Oncology

Charleston, South Carolina, 29414, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• Barr PM, Saylors GB, Spurgeon SE, Cheson BD, Greenwald DR, O'Brien SM, Liem AK, Mclntyre RE, Joshi A, Abella-Dominicis E, Hawkins MJ, Reddy A, Di Paolo J, Lee H, He J, Hu J, Dreiling LK, Friedberg JW. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL. Blood. 2016 May 19;127(20):2411-5. doi: 10.1182/blood-2015-12-683516. Epub 2016 Mar 11.

  PMID: 26968534 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia; Lymphoma; Waldenstrom Macroglobulinemia

Interventions

6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine; idelalisib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Limitations and Caveats

As a result of the early termination of the trial for safety, the efficacy endpoints were not evaluable due to insufficient treatment exposure.

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 2
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2013
• First Posted: February 21, 2013
• Study Start: June 20, 2013
• Primary Completion: January 1, 2015
• Study Completion: December 22, 2016
• Last Updated: June 2, 2020
• Results First Posted: June 2, 2020

Record last verified: 2020-05

Locations

US (13)