An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

EBV-Positive DLBCL, NOS Clinical Trial

— NAVAL-1  

Official title:

An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05011058
• Other study ID #: VT3996-202
• Status: Recruiting
• Phase: Phase 2
• Start date: May 28, 2021
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: Viracta Therapeutics, Inc.
• Contact: Strait Hicklin
• Phone: 858-400-8470
• Email: ClinicalTrials[@]Viracta.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas

Description:

Patients with EBV-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with EBV-negative disease. Nanatinostat is a selective class I HDAC inhibitor which induces EBV lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. This open-label, multicenter, multinational, single-arm, Phase 2 basket study employs a Simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with EBV+ relapsed/refractory lymphomas: 1. EBV+ diffuse large B-cell lymphoma (DLBCL, NOS) 2. Peripheral T-cell lymphoma (PTCL), including PTCL-NOS and AITL 3. Post-transplant lymphoproliferative disorder (PTLD) 4. EBV+ lymphoproliferative disorders other than the above, including Extranodal NK/T-cell lymphoma (ENKTL)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• EBV+ DLBCL, NOS and PTCL, NOS, and AITL: Relapsed/refractory disease following 1 or more prior systemic therapy(ies) with curative intent.
• For EBV+ PTLD patients: Relapsed/refractory disease following 1 prior therapy and must have received at least 1 course of an anti-CD20 immunotherapy. For patients with EBV+ PTLD only, age 12 years and older and weighing greater than 40 kg (Adolescent, Adult, Older Adult) are allowed
• For other EBV+ relapsed/refractory lymphoma: Following at least 1 course of an anit-CD20 immunotherapy and at least 1 course of anthracycline-based chemotherapy (unless contraindicated)
• No available therapies in the opinion of the Investigator
• Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T therapy
• Measurable disease per Cheson 2007
• ECOG performance status 0, 1, 2
• Adequate bone marrow function

Key Exclusion Criteria:

• Presence or history of CNS involvement by lymphoma
• Systemic anticancer therapy or CAR-T within 21 days
• Antibody (anticancer) agents within 28 days
• Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant
• Less than 90 days from prior allogeneic transplant.
• Daily corticosteroids (=20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1
• Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir.
• Active infection requiring systemic therapy (excluding viral upper respiratory tract infections).

Related Conditions & MeSH terms

• EBV Associated Lymphoma
• EBV Related Non-Hodgkin's Lymphoma
• EBV-Positive DLBCL, NOS
• EBV-Related PTLD
• Epstein-Barr Virus Associated Lymphoproliferative Disorder
• Epstein-Barr Virus Infections
• Lymphoma
• Lymphoproliferative Disorders

Intervention

Drug:
• Nanatinostat in combination with valganciclovir
Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles Other name: VRx-3996 Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Brazil	CEPEVILLE - Instituto Joinvilense de Hematologia e Oncologia	Joinville
Brazil	Ruschel Medicina e Pesquisa Clinica	Rio De Janeiro
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André
Brazil	CIPE Centro Internacional de Pesquisa - AC Camargo Cancer Center	São Paulo
Brazil	HCFMUSP - Hospital das Clínicas da Faculdade de Medicina Universidade de São Paulo	São Paulo
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hôpital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer Agency	Vancouver	British Columbia
France	Institut Bergonié	Bordeaux Cedex	Aquitaine
France	Centre Hospitalier Départemental Vendée	La Roche-sur-Yon	Pays De La Loire
France	Centre Hospitalier Universitaire Limoges	Limoges cedex	Limousin
France	Paoli-Calmettes Institute	Marseille
France	Hôpital Saint-Eloi	Montpellier Cedex 5	Provence Alpes Cote d'Azur
France	Henri Mondor University Hospital	Paris
France	Hôpital Universitaire Pitié Salpêtrière	Paris	Ile-de-France
France	Hôpital Haut-Lévêque	Pessac	Nouvelle-Aquitaine
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite	Rhone-Alps
Germany	Evangelisches Diakonie Hospital (DIAKO)	Bremen
Germany	Klinikum Chemnitz	Chemnitz	Saxony
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Martin-Luther-Universität	Halle
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinik für Hämatologie und Onkologie, UKSH Campus Lübeck	Lübeck
Germany	Universitatsmedizin Mannheim	Mannheim
Germany	Klinikum Oldenburg	Oldenburg	Niedersachsen
Germany	Universitätsklinikum Würzburg	Würzburg	Bavaria
Hong Kong	Queen Mary Hospital/University of Hong Kong	Hong Kong
Israel	Hadassah Medical Center, Ein Kerem Hospital	Jerusalem
Italy	Centro di Riferimento Oncologico	Aviano	Pordenone
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi	Bologna
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milan
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu	Gyeongsangbugdo
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Malaysia	University of Malaya	Kuala Lumpur
Malaysia	Sarawak General Hospital / Hospital Umum Sarawak	Kuching
Singapore	National Cancer Centre Singapore	Singapore
Singapore	Oncocare Cancer Center	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Jimenez Diaz Foundation University Hospital	Madrid
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital - Taipei	Taipei
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei City	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou Branch	Taoyuan City
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Kings College Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	St. Vincent Healthcare Cancer Center	Billings	Montana
United States	The University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ohio State University: Wexner Medical Center	Columbus	Ohio
United States	Harold C. Simmons Comprehensive Cancer Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Duke Cancer Institute	Durham	North Carolina
United States	John Theurer Cancer Center: Hackensack Univeristy	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	David Geffen School of Medicine - UCLA	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center - New York	New York	New York
United States	University of California Irvine	Orange	California
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	Sidney Kimmel Cancer Center - Jefferson Health	Philadelphia	Pennsylvania
United States	Scripps MD Anderson Cancer Center	San Diego	California
United States	UCSF Hematology and Blood and Marrow Transplant	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	The Oncology Institute of Hope and Innovation	Torrance	California
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Viracta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Hong Kong,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Assessed by an Independent Review Committee (IRC) per the 2007 International Working Group Response Criteria (IWGRC)	Approximately 3 years
Secondary	Duration of response (DOR)		Approximately 3 years
Secondary	Time to next anti-lymphoma treatment (TTNLT)		Approximately 3 years
Secondary	Progression-free survival (PFS)		Approximately 3 years
Secondary	Time to progression (TTP)		Approximately 3 years
Secondary	Overall survival		Approximately 3 years
Secondary	Incidence and severity of treatment-emergent adverse events		Approximately 28 days following the last dose
Secondary	Pharmacokinetic parameter - time to maximum plasma concentration [tmax],		Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)
Secondary	Pharmacokinetic parameter - maximum plasma concentration [Cmax]		Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)
Secondary	Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC]		Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)