A Phase 1b Study Evaluating GS-9820 in Subjects With Lymphoid Malignancies

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01705847

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

9.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to determine the appropriate dosing regimen of GS-9820 in subjects with lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.

Condition or Disease	Intervention/Treatment	Phase
Lymphoid Malignancies	Drug: GS-9820	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GS-9820 in Subjects With Lymphoid Malignancies

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GS-9820 Participants will be sequentially enrolled at progressively higher dose levels to receive GS-9820 administered twice a day. Escalation will proceed to the maximum tolerated dose (MTD), defined as the highest tested dose associated with a rate of dose-limiting toxicities (DLT) of < 33% during the first 4 weeks of therapy.	Drug: GS-9820 GS-9820 tablets containing 200 mg of GS-9820 administered orally Other Names: CAL-120

Arm

Intervention/Treatment

Experimental: GS-9820

Participants will be sequentially enrolled at progressively higher dose levels to receive GS-9820 administered twice a day. Escalation will proceed to the maximum tolerated dose (MTD), defined as the highest tested dose associated with a rate of dose-limiting toxicities (DLT) of < 33% during the first 4 weeks of therapy.

Drug: GS-9820

GS-9820 tablets containing 200 mg of GS-9820 administered orally

Other Names:

CAL-120

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) [Up to 4 weeks]
MTD will be assessed to determine the appropriate dosing regimens for use in future clinical trials of GS-9820 in subjects with lymphoid malignancies.

Secondary Outcome Measures

Overall safety [Up to 5 years]
Overall safety will be assessed by overall safety profile, enumeration and description of any dose-limiting toxicities, serious adverse events, or adverse events leading to discontinuation of study drug.
Pharmacokinetic parameters of GS-9820 as measured by Cmax, Tmax, Ctrough, and AUC [Baseline to Day 29]
Cmax is defined as the maximum concentration of drug Tmax is defined as the time of Cmax Ctrough is defined as the trough concentration AUC is defined as the area under the plasma concentration versus time curve
Pharmacodynamics to measure changes in the phosphatidylinositol 3-kinase (P13K) delta pathway activation and changes in plasma concentration of disease-associated chemokines and cytokines [Baseline to Day 29]
Tumor control [Up to 5 years]
Tumor control as assessed by overall response rate (ORR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), percent change in lymph node area, lymph node response rate, splenomegaly response rate, ALC response rate, hepatomegaly response rate, platelet response rate, hemoglobin response rate, and neutrophil response rate.
Patient well-being assessed using changes in baseline in HRQL (health related quality of life questionnaire) domain and symptom scores based on the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym) [Up to 5 years]
Drug exposure [Up to 5 years]
Drug administration for GS-9820 as assessed by prescribing records and GS-9820 compliance as assessed by quantification of used and unused drug.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Previously treated recurrent B-cell iNHL, DLBCL, MCL, HL or CLL
Measurable lymphadenopathy
Requires therapy

Exclusion Criteria:

Recent history of a major non-lymphoid malignancy
Evidence of ongoing infection
Concurrent participation in another therapeutic clinical trial

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	VU Medical Center (VUmc)	Amsterdam	Netherlands	1081 HV
2	Academic Medical Center	Amsterdam	Netherlands	1105 AZ
3	St. Antonius Hospital	Nieuwegein	Netherlands	3435 CM
4	Erasmus MC - Daniel den Hoed Cancer Center	Rotterdam	Netherlands	3075 EA