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TerminatedNCT04390113Updated May 14, 2024Results posted

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

A Phase 3 interventional study of Posoleucel (ALVR105) and Placebo in BK Virus Infection and Hemorrhagic Cystitis, sponsored by AlloVir. Terminated at 56 sites in 7 countries. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2024-05-14.

Sponsored by AlloVir · Phase 3, Interventional, and Treatment

Why this study was terminated
Study discontinued as DSMB determined it was futile. No safety concerns were noted.
Phase
Phase 3
Study type
Interventional
Enrollment
97
Allocation
Randomized
Ages
1 Year and older
Sex
All
01

Study summary

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

Read the 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).

02

Conditions studied

  • BK Virus Infection
  • Hemorrhagic Cystitis

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Keywords

  • Allogeneic Hematopoietic Cell Transplant
  • ALVR105
  • Posoleucel
03

Who can participate

Ages eligible
1 Year and older
Sexes eligible
All
Accepts healthy volunteers
No

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.

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
97 participants (actual)

Study arms

  • Placebo comparator
    Placebo

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

    Biological: Placebo

  • Experimental
    Posoleucel (ALVR105)

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

    Biological: Posoleucel (ALVR105)

Interventions

  • BiologicalPosoleucel (ALVR105)

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

  • BiologicalPlacebo

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

05

What researchers measure

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.

    Time frame: Up to 24 weeks

Secondary outcomes

  1. Time Until Bladder Pain is Resolved

    Time frame: Until event occurrence through Week 24

  2. Days in the Hospital for Any Reason

    Time frame: Until event occurrence through Week 24

  3. 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.

    Time frame: Up to 24 weeks

  4. 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.

    Time frame: Up to 24 weeks

  5. Time to Resolution for All Target Viruses

    Time frame: Until event occurrence through Week 24

  6. Average Daily Bladder Pain

    Time frame: Until event occurrence through Week 6

06

Results

Posted May 14, 2024
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.

Participant flow

Participants were enrolled from March 2021 to Jan 2024 across 57 study centers in the United States, Canada, France, Italy, Spain, Sweden, the United Kingdom and South Korea.

Participant flow — Overall Study
MilestonePosoleucel (ALVR105)Placebo
Started5740
Completed3726
Not completed2014
Withdrew: Not treated01
Withdrew: Adverse event10
Withdrew: Death21
Withdrew: Physician decision13
Withdrew: Study terminated by sponsor53
Withdrew: Withdrawal by subject105
Withdrew: Other10
Withdrew: Missing01

Outcome measures

PrimaryTime 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.

Time frame:
Up to 24 weeks
Reported as:
Median · Days
Time to Resolution of Macroscopic Hematuria
DaysPosoleucel (ALVR105)Placebo
Time to Resolution of Macroscopic Hematuria36 (22.0 to 63.0)31 (18.0 to 63.0)
Statistical analysis
  • Posoleucel (ALVR105) vs Placebo · Log Rank · p = 0.6253 · Hazard ratio (hr): 0.92 · 95% CI 0.55 to 1.55
SecondaryTime Until Bladder Pain is Resolved
Time frame:
Until event occurrence through Week 24

No measurements were reported for this outcome.

SecondaryDays in the Hospital for Any Reason
Time frame:
Until event occurrence through Week 24

No measurements were reported for this outcome.

SecondaryNumber 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.

Time frame:
Up to 24 weeks
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Acute Graft Versus Host Disease (GVHD)
ParticipantsPosoleucel (ALVR105)Placebo
Number of Participants With Treatment Emergent Acute Graft Versus Host Disease (GVHD)119
SecondaryNumber 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.

Time frame:
Up to 24 weeks
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)
ParticipantsPosoleucel (ALVR105)Placebo
Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)10
SecondaryTime to Resolution for All Target Viruses
Time frame:
Until event occurrence through Week 24

No measurements were reported for this outcome.

SecondaryAverage Daily Bladder Pain
Time frame:
Until event occurrence through Week 6

No measurements were reported for this outcome.

Adverse events

Collected over Up to 24 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Posoleucel (ALVR105)2/57 (3.5%)28/57 (49.1%)54/57 (94.7%)
Placebo1/40 (2.5%)19/39 (48.7%)36/39 (92.3%)
Most frequent serious events
Showing 10 of 75
Most frequent serious events
EventPosoleucel (ALVR105)Placebo
Respiratory failureRespiratory, thoracic and mediastinal disorders2/573/39
PyrexiaGeneral disorders2/573/39
PneumoniaInfections and infestations4/571/39
NauseaGastrointestinal disorders3/570/39
VomitingGastrointestinal disorders3/570/39
Viral haemorrhagic cystitisInfections and infestations2/572/39
HypoxiaRespiratory, thoracic and mediastinal disorders1/572/39
Acute kidney injuryRenal and urinary disorders1/572/39
Febrile neutropeniaBlood and lymphatic system disorders1/572/39
HypotensionVascular disorders0/572/39
Most frequent other events
Showing 10 of 84
Most frequent other events
EventPosoleucel (ALVR105)Placebo
AnaemiaBlood and lymphatic system disorders4/579/39
DiarrhoeaGastrointestinal disorders13/578/39
HypokalaemiaMetabolism and nutrition disorders9/578/39
PyrexiaGeneral disorders11/578/39
NauseaGastrointestinal disorders11/573/39
Abdominal painGastrointestinal disorders6/577/39
RashSkin and subcutaneous tissue disorders0/577/39
Blood creatinine increasedInvestigations6/576/39
Acute graft versus host disease in intestineImmune system disorders8/573/39
Urinary tract infectionInfections and infestations3/575/39

Baseline characteristics

Age, Continuous
Age, Continuous(years)Posoleucel (ALVR105)PlaceboTotal
Mean44.9 ± 16.5947.0 ± 16.6045.8 ± 16.54
Sex: Female, Male
Sex: Female, Male(Participants)Posoleucel (ALVR105)PlaceboTotal
Female191635
Male382462
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Posoleucel (ALVR105)PlaceboTotal
Hispanic or Latino13720
Not Hispanic or Latino383068
Unknown or Not Reported639
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Posoleucel (ALVR105)PlaceboTotal
American Indian or Alaska Native101
Asian7310
Native Hawaiian or Other Pacific Islander202
Black or African American9211
White333063
More than one race000
Unknown or Not Reported5510
07

Study locations

56 sites
  • City of Hope National Medical Center
    Duarte, California 91010, United States
  • Children's Hospital of Los Angeles
    Los Angeles, California 90027, United States
  • Yale University School of Medicine - Yale Cancer Center
    New Haven, Connecticut 06520, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010, United States
  • University of Miami
    Miami, Florida 33136, United States
  • Moffitt
    Tampa, Florida 33612, United States
  • Northside Hospital
    Atlanta, Georgia 30342, United States
  • Northwestern Memorial Hospital
    Chicago, Illinois 60611, United States
  • University of Kansas Cancer Center
    Kansas City, Kansas 66160, United States
  • Johns Hopkins Medicine
    Baltimore, Maryland 21287, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02215, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Children's Mercy Hospital - Kansas City
    Kansas City, Missouri 64108, United States
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Roswell Park Comprehensive Cancer Center
    Buffalo, New York 14263, United States
  • University Hospitals Cleveland Medical Center
    Cleveland, Ohio 44106, United States
  • Ohio State University Medical Center (OSUMC)
    Columbus, Ohio 43210, United States
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
  • Children's Hospital of Philadelphia (CHOP)
    Philadelphia, Pennsylvania 19104, United States
  • The University of Texas Southwestern Medical Center
    Dallas, Texas 75390, United States
  • Virginia Commonwealth University
    Richmond, Virginia 23284, United States
  • Fred Hutchinson Cancer Research Center
    Seattle, Washington 98109, United States
  • Froedtert Hospital and the Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • 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, France
  • 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, Italy
  • 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, Korea, Republic of
  • 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, Spain
  • Karolinska University Hospital
    Stockholm, Sweden
  • 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 Kingdom
08

References and documents

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. PubMed 28783452 ↗

Study documents

  • Study protocol · Feb 23, 2022
  • Statistical analysis plan · Nov 14, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04390113
Lead sponsor
AlloVir
Responsible party
Sponsor
First posted
May 15, 2020
Start date
Mar 18, 2021
Primary completion
Jan 30, 2024
Completion
Jan 30, 2024
Results posted
May 14, 2024
Last update
May 14, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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