Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV+ Lymphoid Malignancies

NCT ID: NCT03397706

Last Updated: 2025-03-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-29

Study Completion Date

2023-05-04

Brief Summary

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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

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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.

Conditions

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Epstein-Barr Virus-Associated Lymphoma Lymphoproliferative Disorders

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1b Dose Escalation

VRx-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

Group Type EXPERIMENTAL

VRx-3996 and valganciclovir

Intervention Type COMBINATION_PRODUCT

second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396)

Phase 2 Expansion - Capsule

VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)

Group Type EXPERIMENTAL

VRx-3996 and valganciclovir

Intervention Type COMBINATION_PRODUCT

second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396)

Phase 2 Expansion - Tablet

VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)

Group Type EXPERIMENTAL

VRx-3996 and valganciclovir

Intervention Type COMBINATION_PRODUCT

second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396)

Interventions

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VRx-3996 and valganciclovir

second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396)

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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nanatinostat ganciclovir Chroma (CHR)-3996

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Viracta Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jill DeFratis Robinson

Role: STUDY_DIRECTOR

Viracta Therapeutics

Locations

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USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

UC Irvine Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

University of Colorado Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Mid Florida Hematology and Oncology Center

Orange City, Florida, United States

Site Status

ASCLEPES Research Centers

Weeki Wachee, Florida, United States

Site Status

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Ruth M Rothstein CORE Center

Chicago, Illinois, United States

Site Status

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States

Site Status

The University of Kansas Cancer Center and Medical Pavilion

Westwood, Kansas, United States

Site Status

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

St. Vincent Healthcare Cancer Center

Billings, Montana, United States

Site Status

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Weill Cornell Medical College - New York Presbyterian Hospital

New York, New York, United States

Site Status

The Ohio State University Wexner Medical Center James Cancer Hospital

Columbus, Ohio, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

Centro de Hematologia e Oncologia da Bahia (CEHON)

Salvador, Estado de Bahia, Brazil

Site Status

Hospital de Cancer de Pernambuco (HCP)

Recife, Pernambuco, Brazil

Site Status

Hospital do Cancer Mae de Deus

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Real e Benemerita Associacao Portuguesa de Beneficencia

São Paulo, São Paulo, Brazil

Site Status

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)

São Paulo, São Paulo, Brazil

Site Status

Hospital Santa Marcelina

São Paulo, São Paulo, Brazil

Site Status

Countries

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United States Brazil

References

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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.

Reference Type DERIVED
PMID: 37530631 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.viracta.com/

Viracta Therapeutics, Inc.

Other Identifiers

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VT3996-201

Identifier Type: -

Identifier Source: org_study_id

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