Clinical trial NCT05305040: Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant
Official title: Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ALVR105 Posoleucel (ALVR105,Viralym-M) Compared to Placebo for the Prevention of AdV, BKV, CMV, EBV, HHV-6, and JCV Infection and/or Disease, in High-Risk Patients After Allogeneic Hematopoietic Cell Transplant
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Adenovirus Infection
BK Virus Infection
Cytomegalovirus Infections
Epstein-Barr Virus Infections
Human Herpes Virus-6 Infection
JC Virus Infection
Keywords: Allogeneic Hematopoietic Cell Transplant
ALVR105
Posoleucel
Viralym-M
Virus-specific T cells (VSTs)
Cytotoxic T Lymphocytes (CTLs)
Lead sponsor: AlloVir
Sponsor class: INDUSTRY
First posted: 2022-03-31
Enrollment: 451
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a Phase 3 study to evaluate posoleucel (ALVR105, Viralym-M); an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets six viral pathogens: BK virus, cytomegalovirus, adenovirus, Epstein-Barr virus, human herpesvirus 6 and JC virus.

Detailed description: This is a Phase 2/3, multicenter, randomized, double-blind, placebo controlled trial comparing posoleucel to placebo for the prevention of infection or disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV in high-risk adult and pediatric patients after allogeneic HCT.

There are 2 parts to the study, a Phase 3 randomized study cohort described in this posting, and an open label Phase 2 cohort described in NCT04693637, which has completed enrollment. In this Phase 3 part, approximately 302 eligible allogeneic HCT recipients will be enrolled and will receive 7 doses of posoleucel or placebo over 12 weeks, followed by a 12 week follow-up period.

Eligibility criteria: Key Inclusion Criteria:

* Any age at the day of screening visit.
* No known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV
* Within 25 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment at time of dosing
* Meet one or more of the following criteria at the time of randomization:

  * Related (sibling) donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B or -DR
  * Haploidentical donor
  * Matched or Mismatched unrelated donor
  * Use of umbilical cord blood as stem cell source
  * Ex vivo graft manipulation resulting in T cell depletion
  * Received anti-thymocyte globulin or alemtuzumab (Campath-1H)

Key Exclusion Criteria:

* History of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization
* Evidence of active Grade \>2 acute GVHD
* Presence of non-minor uncontrolled or progressive bacterial, viral or fungal infections
* Known history or current (suspected) diagnosis of Grade ≥3 CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies
* Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose \>1.0 mg/kg/day) within 24 hours prior to dosing
* Relapse of primary malignancy other than minimal residual disease

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 14
timeFrame: Through Week 14
Secondary outcomes:
measure: Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 26
timeFrame: Through Week 26
measure: Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus
timeFrame: Through Week 14
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Children's of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Childrens National Health System
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida (UF) - Gainesville
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Hospital Simon Comprehensive Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital Cancer Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah/Primary Childrens Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Heidelberg
country: Australia
facility: Austin Health
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Brugge
country: Belgium
facility: A.Z. Sint-Jan Brugge Oostende AV
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet and the Childrens Hospital
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg and Leuven
city: Calgary
country: Canada
facility: Alberta Children's Hospital
city: Montréal
country: Canada
facility: Cellular Therapy Program - CHU Sainte-Justine (McGill)
city: Montréal
country: Canada
facility: Hopital Maisonneve Rosemont
city: Toronto
country: Canada
facility: The Hospital for Sick Children Blood & Marrow Transplant / Cellular Therapy Program
city: Toronto
country: Canada
facility: UHN Blood and Marrow Transplant (BMT) Program (Princess Margaret) Cancer Center
city: Vancouver
country: Canada
facility: Leukemia/ BMT Program of British Columbia - Vancouver General Hospital
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: AP-HP Hopital Saint-Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital Universitaire Robert Debre
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Toulouse
country: France
facility: IUCT-Oncopole
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico San Matteo
city: Roma
country: Italy
facility: IRCSS Ospedale Pediatrico Bambino Gesu
city: Rome
country: Italy
facility: University of Sacred Heart Policlinico A. Gemelli
city: Rozzano
country: Italy
facility: Humanitas Cancer Center
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona (AOUI)
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Adana
country: Turkey
facility: Baskent Adana Hospital
city: Ankara
country: Turkey
facility: Ankara Onkoloji Egitim Ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Ankara University Hospital
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Hospital
city: Antalya
country: Turkey
facility: Medical Park Hospital
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Kocaeli
country: Turkey
facility: Anadolu Medical Center Hospital
city: Malatya
country: Turkey
facility: Inonu University Turgut Özal Medical Centre
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol - Bristol Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital - Glasgow
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
Study officials:
References:
citation: Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-HCT: Results from an Open-Label Cohort of a Phase 2 Trial Sanjeet S Dadwal, Michael Shuster, Gary Douglas Myers, Keith Boundy, Marshelle Warren, Elizabeth Stoner, Thuy Truong, Joshua A. Hill Blood (2021) 138 (Supplement 1): 1760.
citation: Tzannou I, Papadopoulou A, Naik S, Leung K, Martinez CA, Ramos CA, Carrum G, Sasa G, Lulla P, Watanabe A, Kuvalekar M, Gee AP, Wu MF, Liu H, Grilley BJ, Krance RA, Gottschalk S, Brenner MK, Rooney CM, Heslop HE, Leen AM, Omer B. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol. 2017 Nov 1;35(31):3547-3557. doi: 10.1200/JCO.2017.73.0655. Epub 2017 Aug 7.