Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified May 2020 by Viracta Therapeutics, Inc.

Sponsor
Viracta Therapeutics, Inc.


Information provided by (Responsible Party)
Viracta Therapeutics, Inc.
ClinicalTrials.gov Identifier
NCT03397706

First received: December 20, 2017
Last updated: May 19, 2020
Last Verified: May 2020
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
Epstein-Barr Virus Associated Lymphoma
Lymphoproliferative Disorders

Drug : VRx-3996
Drug : Valganciclovir
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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
Masking: None (Open Label)
Primary Purpose: Treatment
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

Further study details as provided by Viracta Therapeutics, Inc.:

Primary Outcome Measures

  • Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
  • Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determine safety and tolerability
  • ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment [ Time Frame: Approximately 2 years ]
    Disease response will be assessed using a combination of physical exam and imaging
Secondary Outcome Measures:
  • Single-dose and steady-state Cmax of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    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 C2 D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15.
  • Single-dose and steady-state AUC of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    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 C2 D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15.
  • Steady-state elimination half-life of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    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 C2 D1 and pre-dose and at hour 2 on C1D2, C1D15, and C2D15.
  • Time to response [ Time Frame: Approximately 6 months ]
    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 [ Time Frame: Up to approximately 2 years ]
    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 [ Time Frame: Up to approximately 2 years ]
    The interval between the date of first study drug administration and the date of PD or death, whichever is first reported

Estimated Enrollment: 80
Study Start Date: March 29, 2018
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 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
Drug: VRx-3996

capsules taken orally once or twice daily

Drug: Valganciclovir

tablets taken orally once or twice daily

Experimental: Phase 2 Dose Expansion
VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
Drug: VRx-3996

capsules taken orally once or twice daily

Drug: Valganciclovir

tablets taken orally once or twice daily

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03397706

Contacts

Contact:   Robert McRae, Vice President, Operations 858-400-8470 ClinicalTrials@Viracta.com

Locations

United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Christine Duran, Study Coordinator    323-865-0371    duran_c@med.usc.edu
Principal Investigator: Anil Tulpule, MD
UC Irvine Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Michelle Perez    714-509-2414    michelrp@uci.edu
Principal Investigator: Elizabeth Brem, MD
United States, Colorado
University of Colorado Anschutz Cancer Pavilion Recruiting
Aurora, Colorado, United States, 80045
Contact: Justin Massingill    720-848-0736    Justin.Massingill@ucdenver.edu
Principal Investigator: Bradley Haverkos, MD
United States, Florida
Mid Florida Hematology and Oncology Center Recruiting
Orange City, Florida, United States, 32763
Contact: Mahesh Nelakurthi    386-774-1223 ext 175    mahesh@aorcorp.com
Principal Investigator: Santosh Nair, MD
United States, Georgia
Georgia Cancer Center at Augusta University Recruiting
Augusta, Georgia, United States, 30912
Contact: Crystal Durden    706-721-0660    CRDurden@augusta.edu
Principal Investigator: Locke Bryan, MD
United States, Illinois
Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Reem Karmali, MD, MS    312-695-0990    reem.karmali@northwestern.edu
Principal Investigator: Reem Karmali, MD, MS
Ruth M Rothstein CORE Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Mieoak Bahk    312-572-4543    mbahk@cookcountyhhs.org
Principal Investigator: Paul Rubenstein, MD
United States, Indiana
Indiana Blood and Marrow Transplantation Recruiting
Indianapolis, Indiana, United States, 46237
Contact: Melanie Coleman    317-528-7298    melanie.coleman@franciscanalliance.org
Principal Investigator: John Edwards, MD
United States, Kansas
The University of Kansas Cancer Center and Medical Pavilion Recruiting
Westwood, Kansas, United States, 66205
Contact: Emily Kelly, Study Coordinator    913-588-2545    ekelly4@kumc.edu
Principal Investigator: Anusha Vallurupalli, MD
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Laura Clark, Study Nurse    410-502-5396    lclark53@jhmi.edu
Principal Investigator: Richard Ambinder, MD
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Vijayalakshmi Donthireddy, MD    vdonthi1@hfhs.org
Contact: Marjorie Wood
Principal Investigator: Vijayalakshmi Donthireddy, MD
United States, New Jersey
John Theurer Cancer Center at Hackensack UMC Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Sabrina Kdiry    551-996-5952    Sabrina.Kdiry@hackensackmeridian.org
Principal Investigator: Tatyana Feldman, MD
United States, New York
Weill Cornell Medical College - New York Presbyterian Hospital Recruiting
New York, New York, United States, 10065
Contact: Jennifer Bourke, Research Nurse    212-746-2844    jeb9097@med.cornell.edu
Principal Investigator: Koen van Besien, MD, PhD
United States, Ohio
The Ohio State University Wexner Medical Center James Cancer Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: Cynthia Jenkins    614-366-0855    cynthia.jenkins@osumc.edu
Principal Investigator: Polina Shindiapina, MD
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Ariel Kobylak    215-955-2810    Ariel.Kobylak@jefferson.edu
Principal Investigator: Onder Alpdogan, MD
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Lovlei McKinnie    215-214-3173    Lovlei.McKinnie@fccc.edu
Principal Investigator: Asya Varshavsky, MD
Brazil
Centro de Hematologia e Oncologia da Bahia (CEHON) Recruiting
Salvador, BA, Brazil, 40110-090
Contact: Débora Santos    +55 (71) 3281-6484    debora.santos@clinicacehon.com.br
Principal Investigator: Ana Luzia Schriefer, MD
Hospital de Cancer de Pernambuco (HCP) Recruiting
Recife, PE, Brazil, 50040-000
Contact: Valeria Lobo Tavares    +55 (71) 3217-8084
Contact: Livia Tavares de Oliveira    +55 (71) 3217-8084
Principal Investigator: Reijane Assis, MD
Hospital do Cancer Mae de Deus Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil
Contact: Gabriela Alerico    +55 (51) 3234-4345    alerico.pesquisa@gmail.com
Principal Investigator: Marcelo Capra, MD
Real e Benemerita Associacao Portuguesa de Beneficencia Recruiting
São Paulo, SP, Brazil, 01321-001
Contact: Gislaine Mancin    +55 (11) 3505-6675    gislaine.mancin@bp.org.br
Principal Investigator: Phillip Scheinberg, MD
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) Recruiting
São Paulo, SP, Brazil, 05403-000
Contact: Maris Sugino    +55 (11) 4573-7631    maris.sugino@hc.fm.usp.br
Principal Investigator: Juliana Pereira, MD
Hospital Santa Marcelina Recruiting
São Paulo, SP, Brazil, 08270-070
Contact: Carlos Opazo    +55 (11) 2217-3766    carlos.opazocpc@santamarcelina.org
Principal Investigator: Jose Oliveira, MD

Sponsors and Collaborators

Viracta Therapeutics, Inc.

Investigators

Study Director: Robert McRae Viracta Therapeutics, Inc.
More Information

More Information

Additional Information:

Viracta Therapeutics, Inc.

Responsible Party: Viracta Therapeutics, Inc.  
ClinicalTrials.gov Identifier: NCT03397706   History of Changes  
Other Study ID Numbers: VT3996-201  
Study First Received: December 20, 2017  
Last Updated: May 19, 2020  
Individual Participant Data    
Plan to Share IPD: No  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Viracta Therapeutics, Inc.:

EBV+ post-transplant lymphoproliferative malignancy
EBV-associated lymphoproliferative disorders associated with acquired immunodeficiency
Relapsed, refractory, EBV+ lymphoid malignancy

Additional relevant MeSH terms:
Lymphoproliferative Disorders
Neoplasms
Valganciclovir

ClinicalTrials.gov processed this data on June 01, 2020
This information is provided by ClinicalTrials.gov.