An Open-Label Phase 2 Trial of Nanatinostat Plus Valganciclovir in Patients With EBV+ Relapsed/Refractory Lymphomas

NCT ID: NCT05011058

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-28
• Study Completion Date: 2025-01-31

Brief Summary

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

Detailed 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. Diffuse large B-cell lymphoma (DLBCL)

2. Extranodal natural killer/T-cell lymphoma (ENKTL)

3. Peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS)

4. Hodgkin lymphoma (HL)

5. Post-transplant lymphoproliferative disorders (PTLD)

6. Human immunodeficiency virus (HIV)-associated lymphomas (HIV-L)

7. EBV+ lymphomas other than the above

The study was terminated prematurely and did not reach its target enrollment.

Conditions

Epstein-Barr Virus Associated Lymphoma; EBV-Positive DLBCL, NOS; EBV-Related Non-Hodgkin Lymphoma; EBV Related PTCL, NOS; EBV-Related Hodgkin Lymphoma; EBV-Related PTLD; EBV-Related Lymphoproliferative Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nanatinostat with Valganciclovir

Patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week with valganciclovir 900 mg orally once daily.

Up to 10 PTCL patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week.

Group Type: EXPERIMENTAL

Nanatinostat in combination with valganciclovir

Intervention Type: DRUG

Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles

Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles

Interventions

Nanatinostat in combination with valganciclovir

Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles

Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles

Intervention Type: DRUG

Other Intervention Names

VRx-3996 in combination with Valcyte

Eligibility Criteria

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

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Viracta Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darrel P Cohen, MD, PhD

Role: STUDY_DIRECTOR

Viracta Therapeutics

Locations

The University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

City of Hope

Duarte, California, United States

David Geffen School of Medicine - UCLA

Los Angeles, California, United States

University of California Irvine

Orange, California, United States

Scripps MD Anderson Cancer Center

San Diego, California, United States

UCSF Hematology and Blood and Marrow Transplant

San Francisco, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

John Theurer Cancer Center: Hackensack Univeristy

Hackensack, New Jersey, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Ohio State University: Wexner Medical Center

Columbus, Ohio, United States

Sidney Kimmel Cancer Center - Jefferson Health

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States

Box Hill Hospital

Melbourne, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

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, , Brazil

Cross Cancer Institute

Edmonton, Alberta, Canada

BC Cancer Agency

Vancouver, British Columbia, Canada

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Institut Bergonié

Bordeaux, Aquitaine, France

Centre Hospitalier Universitaire Limoges

Limoges, Limousin, France

Hôpital Haut-Lévêque

Pessac, Nouvelle-Aquitaine, France

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Rhone-Alps, France

Henri Mondor University Hospital

Paris, , France

Hôpital Universitaire Pitié Salpêtrière

Paris, Île-de-France Region, France

Universitätsklinikum Würzburg

Würzburg, Bavaria, Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Hadassah Medical Center, Ein Kerem Hospital

Jerusalem, , Israel

Istituto Clinico Humanitas

Rozzano, Milan, 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

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Sarawak General Hospital / Hospital Umum Sarawak

Kuching, , Malaysia

National Cancer Centre Singapore

Singapore, , Singapore

Oncocare Cancer Center

Singapore, , Singapore

Singapore General Hospital

Singapore, , Singapore

Gachon University Gil Medical Center

Incheon, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospitalet de Llobregat

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Jimenez Diaz Foundation University Hospital

Madrid, , Spain

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan, , Taiwan

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Australia; Brazil; Canada; France; Germany; Israel; Italy; Malaysia; Singapore; South Korea; Spain; Taiwan; United Kingdom

References

Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

Reference Type: BACKGROUND

PMID: 17242396 (View on PubMed)

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

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VT3996-202

Identifier Type: -

Identifier Source: org_study_id