Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant

Cytomegalovirus Infections Clinical Trial

— Prevent  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05305040
• Other study ID #: P-105-202 Phase 3
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: March 21, 2022
• Est. completion date: January 31, 2024

Study information

• Verified date: February 2024
• Source: AlloVir
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 378
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus Infection
• BK Virus Infection
• Communicable Diseases
• Cytomegalovirus Infections
• Epstein-Barr Virus Infections
• Human Herpes Virus-6 Infection
• Infections
• JC Virus Infection
• Virus Diseases

Intervention

Biological:
• Posoleucel (ALVR105)
Administered as 2-4 milliliter infusion, visually identical to placebo
• Placebo
Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Austin Health	Heidelberg
Australia	Royal Brisbane and Women's Hospital	Herston
Australia	Royal Melbourne Hospital	Parkville
Australia	Queensland Children's Hospital	South Brisbane
Australia	Westmead Hospital	Westmead
Belgium	A.Z. Sint-Jan Brugge Oostende AV	Brugge
Belgium	Institut Jules Bordet and the Childrens Hospital	Bruxelles
Belgium	University Hospital Gasthuisberg and Leuven	Leuven
Canada	Alberta Children's Hospital	Calgary
Canada	Cellular Therapy Program - CHU Sainte-Justine (McGill)	Montréal
Canada	Hopital Maisonneve Rosemont	Montréal
Canada	The Hospital for Sick Children Blood & Marrow Transplant / Cellular Therapy Program	Toronto
Canada	UHN Blood and Marrow Transplant (BMT) Program (Princess Margaret) Cancer Center	Toronto
Canada	Leukemia/ BMT Program of British Columbia - Vancouver General Hospital	Vancouver
France	Centre Hospitalier Regional Universitaire de Lille	Lille
France	CHU de Nantes	Nantes
France	AP-HP Hopital Saint-Louis	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Universitaire Robert Debre	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	IUCT-Oncopole	Toulouse
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Ospedale San Raffaele	Milan
Italy	Fondazione I.R.C.C.S. Policlinico San Matteo	Pavia
Italy	IRCSS Ospedale Pediatrico Bambino Gesu	Roma
Italy	University of Sacred Heart Policlinico A. Gemelli	Rome
Italy	Humanitas Cancer Center	Rozzano
Italy	Azienda Ospedaliera Universitaria Integrata Verona (AOUI)	Verona
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Spain	Institut Catala d'Oncologia	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Turkey	Acibadem Adana Hospital	Adana
Turkey	Baskent Adana Hospital	Adana
Turkey	Ankara Onkoloji Egitim Ve Arastirma Hastanesi	Ankara
Turkey	Ankara University Hospital	Ankara
Turkey	Gazi University Medical Faculty Hospital	Ankara
Turkey	Medical Park Hospital	Antalya
Turkey	Ege University Medical Faculty	Izmir
Turkey	Anadolu Medical Center Hospital	Kocaeli
Turkey	Inonu University Turgut Özal Medical Centre	Malatya
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	University Hospitals Bristol - Bristol Hospital for Children	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Queen Elizabeth University Hospital - Glasgow	Glasgow
United Kingdom	Great Ormond Street Hospital for Children	London
United States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham Children's of Alabama	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Carolinas Medical Center/Levine	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	City of Hope	Duarte	California
United States	University of Florida (UF) - Gainesville	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University Hospital Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Hospital	Kansas City	Kansas
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Yale University School of Medicine - Yale Cancer Center	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah/Primary Childrens Hospital	Salt Lake City	Utah
United States	University of California San Francisco - Benioff Children's Hospital	San Francisco	California
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stony Brook University Hospital Cancer Center	Stony Brook	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Childrens National Health System	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AlloVir

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Korea, Republic of,  Spain,  Turkey,  United Kingdom, 

References & Publications (2)

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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of clinically significant infections or episodes of end-organ disease		Through Week 14
Secondary	Number of clinically significant infections or episodes of end-organ disease		Through Week 26
Secondary	Number of clinically significant infections or episodes of end-organ disease due to each virus		Through Week 14 and 25
Secondary	Incidence of Adverse Events		Through Week 26
Secondary	Overall and Non-Relapse Mortality		Through Week 26