Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of GS-9901 in Adults With Relapsed or Refractory Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, or Small Lymphocytic Lymphoma

A Phase 1b Dose-escalation Study Evaluating the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of GS-9901 in Subjects With Relapsed or Refractory Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, or Small Lymphocytic Lymphoma

This study will evaluate the safety and tolerability of GS-9901 monotherapy in adults with follicular lymphoma (FL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), or small lymphocytic lymphoma (SLL). The study will also characterize the pharmacokinetic (PK) profile of GS-9901, determine the appropriate dosing regimen of GS-9901 for use in future clinical trials, and to evaluate the efficacy of GS-9901 monotherapy in adults with FL, MZL, CLL, or SLL.

Study Overview

• Status: Terminated
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: GS-9901

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Fresno, California, United States, 93720
      • Cancer Care Center of Fresno
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Cancer Center Central Connecticut
  • District of Columbia
    • Washington, District of Columbia, United States, 02007
      • Lombardi Cancer Center-Georgetown University
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of FL, MZL, SLL, or CLL (meeting International Workshop on CLL [IWCLL] Criteria, 2008) as documented by medical records and with histology based on criteria established by the World Health Organization

  • FL Grades 1, 2, or 3a
  • SLL with absolute lymphocyte count of < 5 x 10^9/L at initial diagnosis
  • MZL (splenic, nodal, or extra-nodal)
• Prior treatment for FL or CLL/SLL with ≥ 1 prior chemotherapy-based or immunotherapy-based regimen with no approved therapies available
• Presence of radiographically measurable lymphadenopathy or extra nodal lymphoid malignancy
• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], or bone marrow parameters [any of Grade 1, 2, or 3 permitted)
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Able to provide written informed consent

Exclusion Criteria:

• History of lymphoid malignancy other than FL, MZL, SLL, or CLL
• History of myelodysplastic syndrome
• History of a non-lymphoid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to start of study therapy, or any other cancer that has been in complete remission for ≥ 5 years
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study therapy
• Ongoing drug-induced pneumonitis
• Ongoing inflammatory bowel disease
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
• History of prior therapy with any inhibitor of serine/threonine kinase (AKT), Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), or spleen tyrosine kinase (SYK)
• Ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GS-9901; Participants will receive one of 6 escalating doses of GS-9901 once daily until unacceptable toxicity, substantial noncompliance, disease progression, pregnancy, initiation of another anti-cancer or experimental therapy, or other protocol-specified reasons for GS-9901 discontinuation.	Drug: GS-9901; GS-9901 tablets administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events (AEs) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)	Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of AEs and clinical laboratory abnormalities not defined as DLTs	Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.	Up to 2 years
Overall response rate	Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).	Up to 2 years
Progression-free survival	Progression-free survival (PFS) is defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause.	Up to 2 years
Duration of response	Duration of response (DOR) is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.	Up to 2 years
PK profile of GS-9901	This endpoint will measure the plasma PK profile of GS-9901. The following parameters will be measured: Cmax: maximum observed concentration of drug in plasma; AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, and 24 hours postdose on Days 1 and 15; predose and 1.5 hours postdose on Days 29, 43, 85, and 169

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 3, 2014
• First Posted (Estimate): October 7, 2014

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Follicular lymphoma (FL); Chronic lymphocytic leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Marginal Zone Lymphoma (MZL); Phosphatidylinositol 3 kinase (PI3K)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Lymphoma, Follicular; Leukemia; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: GS-US-325-1348; 2014-005441-53 (EudraCT Number)