Clinical trial NCT02258555: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-10-07
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of adverse events (AEs) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Occurrence of AEs and clinical laboratory abnormalities not defined as DLTs
timeFrame: Up to 2 years
measure: Overall response rate
timeFrame: Up to 2 years
measure: Progression-free survival
timeFrame: Up to 2 years
measure: Duration of response
timeFrame: Up to 2 years
measure: PK profile of GS-9901
timeFrame: 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
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Fresno
country: United States
facility: Cancer Care Center of Fresno
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Southington
country: United States
facility: Cancer Center Central Connecticut
state: Connecticut
city: Washington
country: United States
facility: Lombardi Cancer Center-Georgetown University
state: District of Columbia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Henry Adewoye, MD
role: STUDY_DIRECTOR
References: