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

Lymphoproliferative Disorders Clinical Trial

Official title:

A Phase 1b/2 Open-Label, Dose Escalation & Expansion Study of Orally Administered VRx-3996 & Valganciclovir in Subjects With Epstein-Barr Virus-Associated Lymphoid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03397706
• Other study ID #: VT3996-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 29, 2018
• Est. completion date: May 4, 2023

Study information

• Verified date: October 2022
• Source: Viracta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 EBV+ lymphomas.

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 PK cohort to investigate the PK parameters of the tablet formulation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 4, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Relapsed/refractory, pathologically confirmed 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 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 qPCR
• Known history of HHV-6 chromosomal integration
• Known history of HIV infection

Related Conditions & MeSH terms

• Epstein-Barr Virus Associated Lymphoma
• Epstein-Barr Virus Infections
• Lymphoproliferative Disorders
• Neoplasms

Intervention

Drug:
• VRx-3996
Taken orally once or twice daily
• Valganciclovir
Taken orally once or twice daily

Locations

Country	Name	City	State
Brazil	Hospital do Cancer Mae de Deus	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Cancer de Pernambuco (HCP)	Recife	PE
Brazil	Centro de Hematologia e Oncologia da Bahia (CEHON)	Salvador	BA
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)	São Paulo	SP
Brazil	Hospital Santa Marcelina	São Paulo	SP
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia	São Paulo	SP
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	University of Colorado Anschutz Cancer Pavilion	Aurora	Colorado
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Vincent Healthcare Cancer Center	Billings	Montana
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Ruth M Rothstein CORE Center	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center James Cancer Hospital	Columbus	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	University of California, Los Angeles	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	UC Irvine Chao Family Comprehensive Cancer Center	Orange	California
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	ASCLEPES Research Centers	Weeki Wachee	Florida
United States	The University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Viracta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion	Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)	Up to approximately 2 years
Primary	Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion		Up to approximately 2 years
Primary	ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment		Up to approximately 2 years
Secondary	Single-dose and steady-state Cmax of VRx-3996 and valganciclovir	PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15	Through Cycle 2 Day 15 (each cycle is 28 days)
Secondary	Single-dose and steady-state AUC of VRx-3996 and valganciclovir	PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15	Through Cycle 2 Day 15 (each cycle is 28 days)
Secondary	Steady-state elimination half-life of VRx-3996 and valganciclovir	PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2, C1D15, and C2D15	Through Cycle 2 Day 15 (each cycle is 28 days)
Secondary	Time to response	The time from the start of first study drug administration to the first overall tumor response observed for subjects who achieved a CR or PR	Approximately 6 months
Secondary	Duration of response	The time interval (days) from date of the first overall response (CR or PR; achieved after study drug administration) to the date of disease progression	Up to approximately 2 years
Secondary	Progression-free survival	The interval between the date of first study drug administration and the date of PD or death, whichever is first reported	Up to approximately 2 years

External Links

•   Viracta Therapeutics, Inc.