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

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

Study Overview

• Status: Terminated
• Conditions: BK Virus Infection; Hemorrhagic Cystitis
• Intervention / Treatment: Biological: Placebo; Biological: Posoleucel (ALVR105)

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).

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lille, France
    • CHU de LILLE - Hopital Claude Huriez
  • Nantes, France
    • CHU de Nantes - Hotel-Dieu
  • Paris, France
    • AP-HP Hôpital Saint-Louis
  • Pierre-Bénite, France
    • HCL Centre Hospitalier Lyon Sud
  • Toulouse, France
    • IUCT-Oncopole
• Italy
  • Firenze, Italy
    • Azienda Ospedaliero-Universitaria Careggi
  • Milano, Italy
    • Irccs Ospedale San Raffaele
  • Milano, Italy
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Roma, Italy
    • Ospedale Pediatrico Bambino Gesu
  • Rome, Italy
    • Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
  • Rozzano, Italy
    • Istituto Clinico Humanitas
  • Verona, Italy
    • Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
• Korea, Republic of
  • Jeongnam, Korea, Republic of
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of
    • Seoul St. Mary's Hospital, The Catholic University of Korea
  • Seoul, Korea, Republic of
    • Pusan National University Hospital
• Spain
  • Barcelona, Spain
    • Hospital Clinic Barcelona
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Málaga, Spain
    • Hospital Regional Universitario de Malaga
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital
• United Kingdom
  • Bristol, United Kingdom
    • University Hospitals Bristol NHS Foundation Trust
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital - Glasgow
  • London, United Kingdom
    • University College London Hospital
  • London, United Kingdom
    • Hammersmith Hospital
  • London, United Kingdom
    • Great Ormond Street Hospital for Children
  • London, United Kingdom
    • The Royal Marsden NHS Foundation Trust
  • Nottingham, United Kingdom
    • Nottingham University Hospitals
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine - Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Moffitt
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital - Kansas City
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center (OSUMC)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia (CHOP)
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)	Biological: Placebo; Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)
Experimental: Posoleucel (ALVR105); Administered as 2-4 milliliter infusion, visually identical to placebo	Biological: Posoleucel (ALVR105); Administered as 2-4 milliliter infusion, visually identical to placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Resolution of Macroscopic Hematuria	Time to macroscopic hematuria resolution is calculated from time of randomization to the first date of observed macroscopic hematuria resolution. Kaplan-Meier estimates reported as median number of days to resolution. Participants were censored at the last follow-up time of any participant in the ITT population if they took definitive therapies to stop bladder bleeding or received treatment for hemorrhagic cystitis with non-PSL VSTs before achieving resolution or deceased. Participants were also censored at last follow up if they failed to achieve resolution by end of study.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Until Bladder Pain is Resolved		Until event occurrence through Week 24
Days in the Hospital for Any Reason		Until event occurrence through Week 24
Number of Participants With Treatment Emergent Acute Graft Versus Host Disease (GVHD)	Grading of acute GVHD is reported according to CTCAE version 5.0 which ranges from Grade 0 (best/no disease) to Grade IV (worst). Participants with Grade I-IV are included.	Up to 24 weeks
Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)	CRS is defined as a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms can be progressive, must include fever at the onset, and may include hypotension, capillary leak (hypoxia), and end organ dysfunction.	Up to 24 weeks
Time to Resolution for All Target Viruses		Until event occurrence through Week 24
Average Daily Bladder Pain		Until event occurrence through Week 6

Collaborators and Investigators

• Sponsor: AlloVir

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2021
• Primary Completion (Actual): January 30, 2024
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Allogeneic Hematopoietic Cell Transplant; ALVR105; Posoleucel
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis; Cystitis, Hemorrhagic
• Other Study ID Numbers: AVM-003-HC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No