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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

Primary Purpose

Follicular Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GS-9901
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring Chronic lymphocytic leukemia (CLL), Follicular lymphoma (FL), Small Lymphocytic Lymphoma (SLL), Phosphatidylinositol 3 kinase (PI3K), Marginal Zone Lymphoma (MZL)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope
  • Cancer Care Center of Fresno
  • Innovative Clinical Research Institute
  • Cancer Center Central Connecticut
  • Lombardi Cancer Center-Georgetown University
  • Northwest Medical Specialties

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GS-9901

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Overall response rate
Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).
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.
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.
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)

Full Information

First Posted
October 3, 2014
Last Updated
October 15, 2015
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02258555
Brief Title
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

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Study Start Date
January 2015 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GS-9901
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GS-9901
Intervention Description
GS-9901 tablets administered orally
Primary Outcome Measure Information:
Title
Occurrence of adverse events (AEs) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)
Description
Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Occurrence of AEs and clinical laboratory abnormalities not defined as DLTs
Description
Overall safety profile will be characterized by number of participants experiencing adverse events or laboratory abnormalities.
Time Frame
Up to 2 years
Title
Overall response rate
Description
Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).
Time Frame
Up to 2 years
Title
Progression-free survival
Description
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.
Time Frame
Up to 2 years
Title
Duration of response
Description
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.
Time Frame
Up to 2 years
Title
PK profile of GS-9901
Description
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)
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry Adewoye, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Cancer Care Center of Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Innovative Clinical Research Institute
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Cancer Center Central Connecticut
City
Southington
State/Province
Connecticut
ZIP/Postal Code
06489
Country
United States
Facility Name
Lombardi Cancer Center-Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
02007
Country
United States
Facility Name
Northwest Medical Specialties
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

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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

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