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

NCT02258555 | Terminated Phase 1

• 2 other identifiers: GS-US-325-13482014-005441-53
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Follicular Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Marginal Zone Lymphoma

Keywords

Chronic lymphocytic leukemia (CLL); Follicular lymphoma (FL); Small Lymphocytic Lymphoma (SLL); Phosphatidylinositol 3 kinase (PI3K); Marginal Zone Lymphoma (MZL)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Occurrence of AEs and clinical laboratory abnormalities not defined as DLTs

  Up to 2 years

• Overall response rate

  Up to 2 years

• Progression-free survival

  Up to 2 years

• Duration of response

  Up to 2 years

• PK profile of GS-9901

  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

Study Arms (1)

GS-9901

EXPERIMENTAL

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

Interventions

GS-9901 DRUG

GS-9901 tablets administered orally

GS-9901

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

Cancer Care Center of Fresno

Fresno, California, 93720, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Cancer Center Central Connecticut

Southington, Connecticut, 06489, United States

Location

Lombardi Cancer Center-Georgetown University

Washington D.C., District of Columbia, 02007, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone

Condition Hierarchy (Ancestors)

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

Study Officials

• Henry Adewoye, MD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2014
• First Posted: October 7, 2014
• Study Start: January 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 19, 2015

Record last verified: 2015-10

Locations

US (6)