Clinical trial NCT05011058: An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Epstein-Barr Virus Associated Lymphoproliferative Disorder
EBV-Related PTLD
EBV Related Non-Hodgkin's Lymphoma
EBV-Positive DLBCL, NOS
EBV Associated Lymphoma
EBV Related PTCL, NOS
Keywords: EBV positive post-transplant lymphoproliferative disorder (PTLD)
EBV lymphoma
Lymphoproliferative Disorders
Epstein-Barr Virus (EBV)
EBV positive T cell lymphoma
EBV positive diffuse large B-cell lymphoma (DLBCL)
EBV positive peripheral T-cell lymphoma (PTCL)
EBV positive PTLD in Pediatrics
Lead sponsor: Viracta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-18
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, single-arm study utilizing a basket trial design.

The study was terminated prematurely and did not reach its target enrollment.
Primary purpose: TREATMENT

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. 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)

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

Eligibility criteria: 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).

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: Approximately 3 years
measure: Time to next anti-lymphoma treatment (TTNLT)
timeFrame: Approximately 3 years
measure: Progression-free survival (PFS)
timeFrame: Approximately 3 years
measure: Time to progression (TTP)
timeFrame: Approximately 3 years
measure: Overall survival
timeFrame: Approximately 3 years
measure: Incidence and severity of treatment-emergent adverse events
timeFrame: Approximately 28 days following the last dose
measure: Pharmacokinetic parameter - time to maximum plasma concentration [tmax],
timeFrame: Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)
measure: Pharmacokinetic parameter - maximum plasma concentration [Cmax]
timeFrame: Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)
measure: Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC]
timeFrame: Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine - UCLA
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Diego
country: United States
facility: Scripps MD Anderson Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Hematology and Blood and Marrow Transplant
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Hackensack
country: United States
facility: John Theurer Cancer Center: Hackensack Univeristy
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University: Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center - Jefferson Health
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Harold C. Simmons Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Institute
state: Utah
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Joinville
country: Brazil
facility: CEPEVILLE - Instituto Joinvilense de Hematologia e Oncologia
city: Rio De Janeiro
country: Brazil
facility: Ruschel Medicina e Pesquisa Clinica
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: São Paulo
country: Brazil
facility: CIPE Centro Internacional de Pesquisa - AC Camargo Cancer Center
city: São Paulo
country: Brazil
facility: HCFMUSP - Hospital das Clínicas da Faculdade de Medicina Universidade de São Paulo
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Bordeaux Cedex
country: France
facility: Institut Bergonié
state: Aquitaine
city: Paris
country: France
facility: Hôpital Universitaire Pitié Salpêtrière
state: Ile-de-France
city: Limoges cedex
country: France
facility: Centre Hospitalier Universitaire Limoges
state: Limousin
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
state: Nouvelle-Aquitaine
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
state: Rhone-Alps
city: Paris
country: France
facility: Henri Mondor University Hospital
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
state: Bavaria
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Jerusalem
country: Israel
facility: Hadassah Medical Center, Ein Kerem Hospital
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
state: Pordenone
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Kuching
country: Malaysia
facility: Sarawak General Hospital / Hospital Umum Sarawak
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Oncocare Cancer Center
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Barcelona
country: Spain
facility: Hospitalet de Llobregat
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Jimenez Diaz Foundation University Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Viracta Therapeutics
name: Darrel P Cohen, MD, PhD
role: STUDY_DIRECTOR
References: