Clinical trial NCT04390113: Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC)
Official title: Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M (ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplant (HCT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: BK Virus Infection
Hemorrhagic Cystitis
Keywords: Allogeneic Hematopoietic Cell Transplant
ALVR105
Posoleucel
Lead sponsor: AlloVir
Sponsor class: INDUSTRY
First posted: 2020-05-15
Enrollment: 97
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC).

Detailed description: The study hypothesis is that the administration of posoleucel (ALVR105) to patients with virus-associated HC will demonstrate superiority for the time to resolution of HC (as measured by resolution of macroscopic hematuria) compared to patients treated with placebo. The primary hypothesis will be tested in patients with BK virus (BKV) viruria to demonstrate superiority over placebo in this population (BK Intent-to-Treat \[ITT\] Population). A supplementary analysis will be conducted in all patients with any virus-associated HC (cytomegalovirus \[CMV\], human herpesvirus 6 \[HHV-6\], Epstein-Barr virus \[EBV\], JC virus \[JCV\], and/or adenovirus \[AdV\]) in order to evaluate efficacy in this broader population (ITT Population).

Eligibility criteria: Key Inclusion Criteria

Participants must meet all of the following criteria in order to be eligible to participate in the study:

* Male or female ≥1 year of age.
* Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior to randomization.
* Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm³ for 3 consecutive laboratory values obtained on different days, and platelet count \>10,000/mm³ at the time of randomization.
* Diagnosed with HC based on the following criteria (all 3 criteria must be met):

  1. Clinical signs and/or symptoms of cystitis.
  2. Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots.
  3. Viruria with ≥1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
* At least 1 identified, suitably matched posoleucel (ALVR105) cell line for infusion is available.

Key Exclusion Criteria

Participants who meet any of the following criteria will be excluded from participation in the study:

* Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose \>0.5 mg/kg/day or equivalent).
* Therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization.
* Evidence of active Grade \>2 acute graft versus host disease (GVHD).
* Uncontrolled or progressive bacterial or fungal infections.
* Uncontrolled or progressive viral infections not targeted by posoleucel (ALVR105).
* Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
* Known or presumed pneumonia secondary to any organism that is not considered to be well-controlled by antimicrobial therapy.
* Pregnant or lactating or planning to become pregnant.

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

Primary outcomes:
measure: Time to Resolution of Macroscopic Hematuria
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Time Until Bladder Pain is Resolved
timeFrame: Until event occurrence through Week 24
measure: Days in the Hospital for Any Reason
timeFrame: Until event occurrence through Week 24
measure: Number of Participants With Treatment Emergent Acute Graft Versus Host Disease (GVHD)
timeFrame: Up to 24 weeks
measure: Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)
timeFrame: Up to 24 weeks
measure: Time to Resolution for All Target Viruses
timeFrame: Until event occurrence through Week 24
measure: Average Daily Bladder Pain
timeFrame: Until event occurrence through Week 6
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: Moffitt
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Kansas City
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center (OSUMC)
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
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: Lille
country: France
facility: CHU de Lille - Hopital Claude Huriez
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
city: Paris
country: France
facility: AP-HP Hopital Saint-Louis
city: Pierre-Bénite
country: France
facility: HCL Centre Hospitalier Lyon Sud
city: Toulouse
country: France
facility: IUCT-Oncopole
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
city: Jeongnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Pusan National University 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, The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital - Glasgow
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
Study officials:
References:
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.