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

BK Virus Infection Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04390113
• Other study ID #: AVM-003-HC
• Status: Terminated
• Phase: Phase 3
• Start date: March 18, 2021
• Est. completion date: January 30, 2024

Study information

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

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 97
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• BK Virus Infection
• Cystitis
• Hemorrhagic Cystitis

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

Sponsors (1)

Lead Sponsor	Collaborator
AlloVir

Countries where clinical trial is conducted

United States,  France,  Italy,  Korea, Republic of,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

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	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	Time Until Bladder Pain is Resolved		Until event occurrence through Week 24
Secondary	Days in the Hospital for Any Reason		Until event occurrence through Week 24
Secondary	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
Secondary	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
Secondary	Time to Resolution for All Target Viruses		Until event occurrence through Week 24
Secondary	Average Daily Bladder Pain		Until event occurrence through Week 6