BK Virus InfectionPhase 3NCT04390113
Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC)
A Phase 3 study testing Posoleucel (ALVR105) in people with BK Virus Infection and Hemorrhagic Cystitis, run by AlloVir at 56 sites in 7 countries.
Trial summary
Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC). Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- BK Virus Infection, Hemorrhagic Cystitis
- What is being tested?
- Posoleucel (ALVR105)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 97 participants
- Where
- 56 sitesin 7 countries
- Study dates
- 18 Mar 2021to 30 Jan 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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).
Show all 10Show fewer
- 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.
Trial locations and contacts
56 sites in 7 countries.
56 sites in 7 countries
United States25 sites
Northside Hospital
Atlanta, Georgia, 30342
Johns Hopkins Medicine
Baltimore, Maryland, 21287
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Massachusetts General Hospital
Boston, Massachusetts, 02215
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Ohio State University Medical Center (OSUMC)
Columbus, Ohio, 43210
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390
City of Hope National Medical Center
Duarte, California, 91010
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Children's Mercy Hospital - Kansas City
Kansas City, Missouri, 64108
Children's Hospital of Los Angeles
Los Angeles, California, 90027
University of Miami
Miami, Florida, 33136
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55455
Yale University School of Medicine - Yale Cancer Center
New Haven, Connecticut, 06520
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23284
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Moffitt
Tampa, Florida, 33612
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Italy7 sites
Azienda Ospedaliero-Universitaria Careggi
Florence
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
Milan
IRCCS Ospedale San Raffaele
Milan
Ospedale Pediatrico Bambino Gesù
Roma
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Rome
Istituto Clinico Humanitas
Rozzano
Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
Verona
South Korea7 sites
Chonnam National University Hwasun Hospital
Jeongnam
Asan Medical Center
Seoul
Pusan National University Hospital
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Seoul St. Mary's Hospital, The Catholic University of Korea
Seoul
Severance Hospital, Yonsei University Health System
Seoul
United Kingdom7 sites
University Hospitals Bristol NHS Foundation Trust
Bristol
Queen Elizabeth University Hospital - Glasgow
Glasgow
Great Ormond Street Hospital for Children
London
Hammersmith Hospital
London
The Royal Marsden NHS Foundation Trust
London
University College London Hospital
London
Nottingham University Hospitals
Nottingham
France5 sites
CHU de Lille - Hopital Claude Huriez
Lille
CHU de Nantes - Hôtel-Dieu
Nantes
AP-HP Hopital Saint-Louis
Paris
HCL Centre Hospitalier Lyon Sud
Pierre-Bénite
IUCT-Oncopole
Toulouse
Spain4 sites
Hospital Clinic Barcelona
Barcelona
Hospital Universitario La Paz
Madrid
Hospital Regional Universitario de Malaga
Málaga
Hospital Universitari i Politecnic La Fe
Valencia
About this study
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)
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).
- Conditions
- BK Virus Infection, Hemorrhagic Cystitis
- Being tested
- Posoleucel (ALVR105), Placebo
- Keywords
- Allogeneic Hematopoietic Cell Transplant, ALVR105, Posoleucel
- Medical subject headings
- Cystitis, Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Posoleucel (ALVR105)Biological
Administered as 2-4 milliliter infusion, visually identical to placebo
PlaceboBiological
Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105) Receives: Biological: Placebo |
| Posoleucel (ALVR105) | Experimental | Administered as 2-4 milliliter infusion, visually identical to placebo Receives: Biological: Posoleucel (ALVR105) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 weeks
Secondary outcomes (6)
Time Until Bladder Pain is Resolved
Measured: Until event occurrence through Week 24
Days in the Hospital for Any Reason
Measured: 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.
Measured: 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.
Measured: Up to 24 weeks
Time to Resolution for All Target Viruses
Measured: Until event occurrence through Week 24
Average Daily Bladder Pain
Measured: Until event occurrence through Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2020
- Study start18 Mar 2021
- Primary completion30 Jan 2024
- Study completion30 Jan 2024
Why it stopped: Study discontinued as DSMB determined it was futile. No safety concerns were noted.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for BK Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- AlloVir
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04390113
- Sponsor's protocol ID
- AVM-003-HC
- Status last verified
- Apr 2024
- First submitted
- 12 May 2020
- Last updated
- 14 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 28783452Vasileiou 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.
PubMed 38597860
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04390113
- Acronym / sponsor ID
- AVM-003-HC
- Conditions
- BK Virus Infection, Hemorrhagic Cystitis
- Keywords
- Allogeneic Hematopoietic Cell Transplant, ALVR105, Posoleucel
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study discontinued as DSMB determined it was futile. No safety concerns were noted.
- Enrolment
- 97 participants (actual)
- Lead sponsor
- AlloVirIndustry (pharma, biotech, devices)
- Study start
- 18 Mar 2021 (actual)
- Primary completion
- 30 Jan 2024 (actual)
- Study completion
- 30 Jan 2024 (actual)
- First posted
- 15 May 2020 (actual)
- Results
- Posted 14 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: PlaceboAdministered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105) |
| Posoleucel (ALVR105) | Experimental | Biological: Posoleucel (ALVR105)Administered as 2-4 milliliter infusion, visually identical to placebo |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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):
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Posoleucel (ALVR105)Administered as 2-4 milliliter infusion, visually identical to placebo | Biological | Posoleucel (ALVR105) |
| PlaceboAdministered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105) | Biological | Placebo |
Primary outcome
Time to Resolution of Macroscopic Hematuria
Time frame: Up to 24 weeks
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.
6 secondary outcomes
Time Until Bladder Pain is Resolved
Time frame: Until event occurrence through Week 24
Days in the Hospital for Any Reason
Time frame: Until event occurrence through Week 24
Number of Participants With Treatment Emergent Acute Graft Versus Host Disease (GVHD)
Time frame: Up to 24 weeks
Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)
Time frame: Up to 24 weeks
Time to Resolution for All Target Viruses
Time frame: Until event occurrence through Week 24
Average Daily Bladder Pain
Time frame: Until event occurrence through Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28783452Tzannou 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.
- Derived from this study: PubMed 38597860Vasileiou 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
56 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Posoleucel (ALVR105) in people with BK Virus Infection and Hemorrhagic Cystitis, run by AlloVir at 56 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Italy, South Korea, United Kingdom, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Resolution of Macroscopic Hematuria (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04390113, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.