Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV+ Lymphoid Malignancies
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
1 other identifier
interventional
64
2 countries
28
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2018
Longer than P75 for phase_1
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 20, 2017
CompletedFirst Posted
Study publicly available on registry
January 12, 2018
CompletedStudy Start
First participant enrolled
March 29, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 4, 2023
CompletedResults Posted
Study results publicly available
March 20, 2025
CompletedMarch 20, 2025
March 1, 2025
5 years
December 20, 2017
January 10, 2025
March 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number (Proportion) of Participants With Adverse Events (AEs)
Number (percentage) of patients experiencing at least one treatment-emergent adverse event, defined as those untoward medical events with onset after the first dose of study drug or existing events that worsened after the first dose during the study
Up to approximately 2 years
Number (Proportion) of Participants With Dose-Limiting Toxicities (DLTs) in Phase 1b
Number (percentage) of patients experiencing a DLT during the first cycle (28 days) of study treatment in Phase 1b, defined as an adverse event (AE) or clinically significant abnormal laboratory value that was at least possibly related to study drugs and was not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness. In addition, to be considered a DLT, the AE had to meet at least one of the following criteria: * Grade 4 anemia unexplained by underlying disease * Grade 4 febrile neutropenia * Grade 4 neutropenia lasting \>5 days * Any other Grade 4 hematologic toxicity (thrombocytopenia, neutropenia, febrile neutropenia, anemia) of any duration * Grade 4 or higher tumor lysis syndrome * Grade 3 or higher thrombocytopenia (with or without bleeding) * Any requirement for platelet transfusion * Grade 3 or higher non-hematologic toxicity despite adequate supportive care * Results in a dose hold of \>7 consecutive days
Cycle 1 (28 days)
Overall Response Rate
Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the Lugano 2014 criteria (Cheson, Bruce D. et al. J Clin Oncology 2014;32(27):3059-68), where CR included complete metabolic response (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions, and PR included partial metabolic response (reduced FDG uptake compared with baseline) or radiologic response (target lesions ≤ 50% decrease in the sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites)
Up to approximately 2 years
Secondary Outcomes (11)
Duration of Response
Up to approximately 2 years
Time to Response
Up to approximately 2 years
Progression-Free Survival
Up to approximately 2 years
Disease Control Rate
Up to approximately 2 years
Overall Survival
Up to approximately 2 years
- +6 more secondary outcomes
Study Arms (3)
Phase 1b Dose Escalation
EXPERIMENTALVRx-3996 (cohort 1) and valganciclovir VRx-3996 (cohort 2) and valganciclovir VRx-3996 (cohort 3) and valganciclovir VRx-3996 (cohort 4) and valganciclovir VRx-3996 (cohort 5) and valganciclovir
Phase 2 Expansion - Capsule
EXPERIMENTALVRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)
Phase 2 Expansion - Tablet
EXPERIMENTALVRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)
Interventions
second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (28)
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California, Los Angeles
Los Angeles, California, 90404, United States
UC Irvine Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of Colorado Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Mid Florida Hematology and Oncology Center
Orange City, Florida, 32763, United States
ASCLEPES Research Centers
Weeki Wachee, Florida, 34607, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Ruth M Rothstein CORE Center
Chicago, Illinois, 60612, United States
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, 46237, United States
The University of Kansas Cancer Center and Medical Pavilion
Westwood, Kansas, 66205, United States
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
St. Vincent Healthcare Cancer Center
Billings, Montana, 59102, United States
John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey, 07601, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, 10065, United States
The Ohio State University Wexner Medical Center James Cancer Hospital
Columbus, Ohio, 43210, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Texas Oncology - Baylor Sammons Cancer Center
Dallas, Texas, 75246, United States
Centro de Hematologia e Oncologia da Bahia (CEHON)
Salvador, Estado de Bahia, 40110-090, Brazil
Hospital de Cancer de Pernambuco (HCP)
Recife, Pernambuco, 50040-000, Brazil
Hospital do Cancer Mae de Deus
Porto Alegre, Rio Grande do Sul, Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia
São Paulo, São Paulo, 01321-001, Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
São Paulo, São Paulo, 05403-000, Brazil
Hospital Santa Marcelina
São Paulo, São Paulo, 08270-070, Brazil
Related Publications (1)
Haverkos B, Alpdogan O, Baiocchi R, Brammer JE, Feldman TA, Capra M, Brem EA, Nair S, Scheinberg P, Pereira J, Shune L, Joffe E, Young P, Spruill S, Katkov A, McRae R, Royston I, Faller DV, Rojkjaer L, Porcu P. Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study. Blood Adv. 2023 Oct 24;7(20):6339-6350. doi: 10.1182/bloodadvances.2023010330.
PMID: 37530631DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Viracta Therapeutics
Study Officials
- STUDY DIRECTOR
Jill DeFratis Robinson
Viracta Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 20, 2017
First Posted
January 12, 2018
Study Start
March 29, 2018
Primary Completion
April 1, 2023
Study Completion
May 4, 2023
Last Updated
March 20, 2025
Results First Posted
March 20, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will not share