Clinical trial NCT03397706: Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV+ Lymphoid Malignancies
Official title: A Phase 1b/2 Open-Label, Dose Escalation & Expansion Study of Orally Administered Viracta (VRx)-3996 & Valganciclovir in Subjects With Epstein-Barr Virus-Associated Lymphoid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Epstein-Barr Virus-Associated Lymphoma
Lymphoproliferative Disorders
Keywords: EBV-associated peripheral T-cell lymphoma
EBV-associated angioimmunoblastic T-cell lymphoma
EBV-associated diffuse large B-cell lymphoma
EBV-associated post-transplant lymphoproliferative disorder
EBV-associated extranodal NK/T-cell lymphoma
EBV-associated Hodgkin lymphoma
EBV-associated non-Hodgkin lymphoma
Lead sponsor: Viracta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-12
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1: dose escalation phase (3+3 design with definitions of dose limiting toxicity) to define a recommended phase 2 dose

Phase 2: dose expansion

Tablet PK Cohort
Primary purpose: TREATMENT

Brief summary: A two part, Phase 1b/2 study to define a recommended Phase 2 dose of VRx-3996 in combination with valganciclovir (Phase 1b) designed to evaluate the efficacy of this combination in relapsed/refractory Epstein-Barr Virus Associated Lymphoma (EBV+ lymphomas).

Detailed description: The purpose of this study is to determine whether VRx-3996 in combination with valganciclovir is safe, determine the side effect profile, and to determine whether this therapy may help patients with EBV-related lymphomas. The study has two phases. Goals of the first phase include determining a safe and tolerable dose that can be administered in phase 2. Goals of the second phase include further evaluating the safety and tolerability of VRx-3996 in combination with valganciclovir, evaluating how the drugs are metabolized in the body, evaluating response rates and other exploratory objectives that will help the researchers evaluate how these drugs work in the body. Participants will receive daily oral doses of the two study drugs and will have multiple study visits where they will have blood collected, physical examinations, and other medical monitoring. Following completion of the Ph2, the study will enroll additional patients into a Tablet Pharmacokinetic (PK) cohort to investigate the PK parameters of the tablet formulation.

Eligibility criteria: Key Inclusion Criteria:

* Relapsed/refractory, pathologically confirmed Epstein-Barr Virus positive (EBV+) lymphoid malignancy or lymphoproliferative disease
* Absence of available therapy with reasonable likelihood of cure or significant clinical benefit
* Adequate hematologic, hepatic and renal function as defined by laboratory assessment

Key Exclusion Criteria:

* Known primary central nervous system (CNS) lymphoma
* Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks
* Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
* Refractory graft versus host disease (GvHD) not responding to treatment
* Known active hepatitis B virus infection
* Circulating hepatitis C virus on quantitative polymerase chain reaction (qPCR)
* Known history of human herpes virus (HHV)-6 chromosomal integration
* Known history of HIV infection

Primary outcomes:
measure: Number (Proportion) of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Number (Proportion) of Participants With Dose-Limiting Toxicities (DLTs) in Phase 1b
timeFrame: Cycle 1 (28 days)
measure: Overall Response Rate
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Duration of Response
timeFrame: Up to approximately 2 years
measure: Time to Response
timeFrame: Up to approximately 2 years
measure: Progression-Free Survival
timeFrame: Up to approximately 2 years
measure: Disease Control Rate
timeFrame: Up to approximately 2 years
measure: Overall Survival
timeFrame: Up to approximately 2 years
measure: Cmax (ng/mL) of VRx-3996
timeFrame: Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
measure: Cmax (ng/mL) of Valganciclovir
timeFrame: Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
measure: Area Under Curve (AUC) 0-t of VRx-3996
timeFrame: Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
measure: AUC 0-t of of Valganciclovir
timeFrame: Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
measure: Half-life of VRx-3996
timeFrame: Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
measure: Half-life of Valganciclovir
timeFrame: Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Orange
country: United States
facility: UC Irvine Chao Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Cancer Pavilion
state: Colorado
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Weeki Wachee
country: United States
facility: ASCLEPES Research Centers
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Ruth M Rothstein CORE Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Westwood
country: United States
facility: The University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Center
state: Montana
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack UMC
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center James Cancer Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Salvador
country: Brazil
facility: Centro de Hematologia e Oncologia da Bahia (CEHON)
state: BA
city: Recife
country: Brazil
facility: Hospital de Cancer de Pernambuco (HCP)
state: PE
city: Porto Alegre
country: Brazil
facility: Hospital do Cancer Mae de Deus
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Real e Benemerita Associacao Portuguesa de Beneficencia
state: SP
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
state: SP
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: SP
Study officials:
affiliation: Viracta Therapeutics
name: Jill DeFratis Robinson
role: STUDY_DIRECTOR
References: