An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas
- Conditions
- EBV Related Non-Hodgkin's LymphomaEBV-Positive DLBCL, NOSEBV Related PTCL, NOSEpstein-Barr Virus Associated Lymphoproliferative DisorderEBV-Related PTLDEBV Associated Lymphoma
- Interventions
- Registration Number
- NCT05011058
- Lead Sponsor
- Viracta Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 102
- 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
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nanatinostat with Valganciclovir Nanatinostat in combination 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.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) Approximately 3 years Assessed by an Independent Review Committee (IRC) per the 2007 International Working Group Response Criteria (IWGRC)
- Secondary Outcome Measures
Name Time Method Time to next anti-lymphoma treatment (TTNLT) Approximately 3 years Progression-free survival (PFS) Approximately 3 years Incidence and severity of treatment-emergent adverse events Approximately 28 days following the last dose Pharmacokinetic parameter - time to maximum plasma concentration [tmax], Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days) 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) Duration of response (DOR) Approximately 3 years Time to progression (TTP) Approximately 3 years Overall survival Approximately 3 years Pharmacokinetic parameter - maximum plasma concentration [Cmax] Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)
Trial Locations
- Locations (62)
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
🇨🇦Montréal, Quebec, Canada
Institut Bergonié
🇫🇷Bordeaux Cedex, Aquitaine, France
Hôpital Universitaire Pitié Salpêtrière
🇫🇷Paris, Ile-de-France, France
Centre Hospitalier Universitaire Limoges
🇫🇷Limoges cedex, Limousin, France
Hôpital Haut-Lévêque
🇫🇷Pessac, Nouvelle-Aquitaine, France
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Bénite, Rhone-Alps, France
Henri Mondor University Hospital
🇫🇷Paris, 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
🇮🇹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
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Sarawak General Hospital / Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Oncocare Cancer Center
🇸🇬Singapore, Singapore
Singapore General Hospital
🇸🇬Singapore, Singapore
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, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Chang Gung Memorial Hospital - Linkou Branch
🇨🇳Taoyuan City, 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