Back to resultsDose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV-Associated Lymphoid Malignancies
Primary Purpose
Epstein-Barr Virus Associated Lymphoma, Lymphoproliferative Disorders
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
VRx-3996
Valganciclovir
Sponsored by
About this trial
This is an interventional treatment trial for Epstein-Barr Virus Associated Lymphoma focused on measuring EBV+ post-transplant lymphoproliferative malignancy, EBV-associated lymphoproliferative disorders associated with acquired immunodeficiency, Relapsed, refractory, EBV+ lymphoid malignancy
Eligibility Criteria
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
Sites / Locations
- USC Norris Comprehensive Cancer Center
- University of California, Los Angeles
- UC Irvine Chao Family Comprehensive Cancer Center
- University of Colorado Anschutz Cancer Pavilion
- Mid Florida Hematology and Oncology Center
- ASCLEPES Research Centers
- Winship Cancer Institute, Emory University
- Georgia Cancer Center at Augusta University
- Northwestern University Feinberg School of Medicine
- Ruth M Rothstein CORE Center
- Indiana Blood and Marrow Transplantation
- The University of Kansas Cancer Center and Medical Pavilion
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Henry Ford Hospital
- St. Vincent Healthcare Cancer Center
- John Theurer Cancer Center at Hackensack UMC
- Memorial Sloan Kettering Cancer Center
- Weill Cornell Medical College - New York Presbyterian Hospital
- The Ohio State University Wexner Medical Center James Cancer Hospital
- Thomas Jefferson University
- Fox Chase Cancer Center
- Texas Oncology - Baylor Sammons Cancer Center
- Centro de Hematologia e Oncologia da Bahia (CEHON)
- Hospital de Cancer de Pernambuco (HCP)
- Hospital do Cancer Mae de Deus
- Real e Benemerita Associacao Portuguesa de Beneficencia
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
- Hospital Santa Marcelina
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Phase 1b Dose Escalation
Phase 2 Dose Expansion
PK Cohort
Arm Description
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
VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
Assessment of VRx-3996 tablet and valganciclovir PK parameters at the RP2D
Outcomes
Primary Outcome Measures
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)
Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion
ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment
Secondary Outcome Measures
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
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
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
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
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
Progression-free survival
The interval between the date of first study drug administration and the date of PD or death, whichever is first reported
Full Information
NCT ID
NCT03397706
First Posted
December 20, 2017
Last Updated
June 1, 2023
Sponsor
Viracta Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03397706
Brief Title
Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV-Associated Lymphoid Malignancies
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
March 29, 2018 (Actual)
Primary Completion Date
June 1, 2023 (Actual)
Study Completion Date
June 1, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Viracta Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 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 PK cohort to investigate the PK parameters of the tablet formulation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus Associated Lymphoma, Lymphoproliferative Disorders
Keywords
EBV+ post-transplant lymphoproliferative malignancy, EBV-associated lymphoproliferative disorders associated with acquired immunodeficiency, Relapsed, refractory, EBV+ lymphoid malignancy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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
PK Cohort
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b Dose Escalation
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 2 Dose Expansion
Arm Type
Experimental
Arm Description
VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
Arm Title
PK Cohort
Arm Type
Experimental
Arm Description
Assessment of VRx-3996 tablet and valganciclovir PK parameters at the RP2D
Intervention Type
Drug
Intervention Name(s)
VRx-3996
Other Intervention Name(s)
Nanatinostat
Intervention Description
Taken orally once or twice daily
Intervention Type
Drug
Intervention Name(s)
Valganciclovir
Intervention Description
Taken orally once or twice daily
Primary Outcome Measure Information:
Title
Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion
Description
Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
Time Frame
Up to approximately 2 years
Title
Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion
Time Frame
Up to approximately 2 years
Title
ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Single-dose and steady-state Cmax of VRx-3996 and valganciclovir
Description
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
Time Frame
Through Cycle 2 Day 15 (each cycle is 28 days)
Title
Single-dose and steady-state AUC of VRx-3996 and valganciclovir
Description
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
Time Frame
Through Cycle 2 Day 15 (each cycle is 28 days)
Title
Steady-state elimination half-life of VRx-3996 and valganciclovir
Description
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
Time Frame
Through Cycle 2 Day 15 (each cycle is 28 days)
Title
Time to response
Description
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
Time Frame
Approximately 6 months
Title
Duration of response
Description
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
Time Frame
Up to approximately 2 years
Title
Progression-free survival
Description
The interval between the date of first study drug administration and the date of PD or death, whichever is first reported
Time Frame
Up to approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill DeFratis Robinson
Organizational Affiliation
Viracta Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
UC Irvine Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Colorado Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Mid Florida Hematology and Oncology Center
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
Facility Name
ASCLEPES Research Centers
City
Weeki Wachee
State/Province
Florida
ZIP/Postal Code
34607
Country
United States
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Georgia Cancer Center at Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Ruth M Rothstein CORE Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Blood and Marrow Transplantation
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
The University of Kansas Cancer Center and Medical Pavilion
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
St. Vincent Healthcare Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59102
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack UMC
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill Cornell Medical College - New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The Ohio State University Wexner Medical Center James Cancer Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Texas Oncology - Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Centro de Hematologia e Oncologia da Bahia (CEHON)
City
Salvador
State/Province
BA
ZIP/Postal Code
40110-090
Country
Brazil
Facility Name
Hospital de Cancer de Pernambuco (HCP)
City
Recife
State/Province
PE
ZIP/Postal Code
50040-000
Country
Brazil
Facility Name
Hospital do Cancer Mae de Deus
City
Porto Alegre
State/Province
Rio Grande Do Sul
Country
Brazil
Facility Name
Real e Benemerita Associacao Portuguesa de Beneficencia
City
São Paulo
State/Province
SP
ZIP/Postal Code
01321-001
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
City
São Paulo
State/Province
SP
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Hospital Santa Marcelina
City
São Paulo
State/Province
SP
ZIP/Postal Code
08270-070
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.viracta.com/
Description
Viracta Therapeutics, Inc.
Learn more about this trial
Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV-Associated Lymphoid Malignancies
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