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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04390113
Other study ID # AVM-003-HC
Secondary ID
Status Terminated
Phase Phase 3
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
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Active, not recruiting NCT05026021 - Prediction of BKvirus Nephropathy Risk by the NEPHROVIR Method in Kidney Transplant Patients With BKvirus Viremia
Recruiting NCT05511779 - Study to Confirm of the Safety and Tolerability of Brincidofovir in Subjects With BK Virus Infection (Viremia) After Kidney Transplantation Phase 2
Recruiting NCT05183490 - R-MVST Cells for Treatment of Viral Infections Phase 1
Active, not recruiting NCT00684372 - BK Viremia After Renal Transplantation N/A
Recruiting NCT06219616 - Prediction of BK Virus Reactivation in Kidney Transplant Recipient N/A
Not yet recruiting NCT05264259 - New Therapeutic Approach Against BK Virus Infection Based on Monoclonal Antibodies
Terminated NCT05305040 - Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant Phase 2/Phase 3
Completed NCT04605484 - Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia Phase 2
Withdrawn NCT02313844 - Most Closely Human Leukocyte Antigen (HLA)-Matched BK Virus-specific T Lymphocytes (Viralym-B) Phase 1
Completed NCT03532971 - Prospective Study of BK Virus Disease After Allogeneic Hematopoietic-cell Transplantation: Defining BK Disease's Natural History, Clinical Spectrum, Immunology, and Outcomes
Recruiting NCT02479698 - Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus Phase 2
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Completed NCT01789203 - Ciprofloxacin for Prevention of BK Infection Phase 4
Completed NCT04693637 - Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant Phase 2/Phase 3
Recruiting NCT05618275 - Role of Neutralizing Antibodies in the Prediction and Treatment of BK Virus Infection in Hematopoietic Stem Cell Allograft Patients at the Pediatric Oncology-hematology Department of the HUS
Recruiting NCT04542733 - The Efficacy of Everolimus With Reduced-dose Tacrolimus Versus Reduced-dose Tacrolimus in Treatment of BK Virus Infection in Kidney Transplantation Recipient N/A
Recruiting NCT05042076 - BK With VST for Kidney Transplant Patients Phase 1
Completed NCT04294472 - A Safety, Pharmacokinetics and Efficacy Study of MAU868 for the Treatment of BK Viremia in Kidney Transplant Recipients Phase 2