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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02258555
• Other study ID #: GS-US-325-1348
• Secondary ID: 2014-005441-53
• Status: Terminated
• Phase: Phase 1
• First received: October 3, 2014
• Last updated: October 15, 2015
• Start date: January 2015
• Est. completion date: August 2015

Study information

• Verified date: October 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Follicular Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Marginal Zone Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• GS-9901
GS-9901 tablets administered orally

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California
United States	Cancer Care Center of Fresno	Fresno	California
United States	Cancer Center Central Connecticut	Southington	Connecticut
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Lombardi Cancer Center-Georgetown University	Washington	District of Columbia
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No