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

NCT04390113 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: AVM-003-HC
• Study Type: interventional
• Target: 97
• Locations: 7 countries
• Sites: 56

Brief Summary

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

Conditions

BK Virus Infection; Hemorrhagic Cystitis

Keywords

Allogeneic Hematopoietic Cell Transplant; ALVR105; Posoleucel

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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)

  Up to 24 weeks

• Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)

  Up to 24 weeks

• Time to Resolution for All Target Viruses

  Until event occurrence through Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)

Biological: Placebo

Posoleucel (ALVR105)

EXPERIMENTAL

Administered as 2-4 milliliter infusion, visually identical to placebo

Biological: Posoleucel (ALVR105)

Interventions

Posoleucel (ALVR105) BIOLOGICAL

Administered as 2-4 milliliter infusion, visually identical to placebo

Posoleucel (ALVR105)

Placebo BIOLOGICAL

Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)

Placebo

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Clinical signs and/or symptoms of cystitis.
• Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AlloVir: lead

Study Sites (56)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Moffitt

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins Medicine

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, 64108, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University Medical Center (OSUMC)

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

CHU de Lille - Hopital Claude Huriez

Lille, France

Location

CHU de Nantes - Hôtel-Dieu

Nantes, France

Location

AP-HP Hopital Saint-Louis

Paris, France

Location

HCL Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

IUCT-Oncopole

Toulouse, France

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, Italy

Location

IRCCS Ospedale San Raffaele

Milan, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Rome, Italy

Location

Istituto Clinico Humanitas

Rozzano, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento

Verona, Italy

Location

Chonnam National University Hwasun Hospital

Jeongnam, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Pusan National University Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Spain

Location

Karolinska University Hospital

Stockholm, Sweden

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, United Kingdom

Location

Queen Elizabeth University Hospital - Glasgow

Glasgow, United Kingdom

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28783452 BACKGROUND

• Vasileiou S, Kuvalekar M, Velazquez Y, Watanabe A, Leen AM, Gilmore SA. Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. Cytotherapy. 2024 Aug;26(8):869-877. doi: 10.1016/j.jcyt.2024.03.012. Epub 2024 Mar 19.

  PMID: 38597860 DERIVED

MeSH Terms

Conditions

Cystitis, Hemorrhagic

Condition Hierarchy (Ancestors)

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

AlloVir decided to discontinue the trial on 22-Dec-2023 following a pre-planned DSMB futility analysis concluding the study was unlikely to meet its primary endpoint; no safety concerns were identified.

Results Point of Contact

• Title: Senior Vice President
• Organization: AlloVir, Inc.

rriese@allovir.com

+1 617-433-2605

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 15, 2020
• Study Start: March 18, 2021
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2024
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); SE (1); GB (7); ES (4); IT (7); KR (7); US (25)