Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant

Study Overview
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Brief Summary
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This is a Phase 3 study to evaluate posoleucel (ALVR105, Viralym-M); an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets six viral pathogens: BK virus, cytomegalovirus, adenovirus, Epstein-Barr virus, human herpesvirus 6 and JC virus.

Detailed Description
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This is a Phase 2/3, multicenter, randomized, double-blind, placebo controlled trial comparing posoleucel to placebo for the prevention of infection or disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV in high-risk adult and pediatric patients after allogeneic HCT. There are 2 parts to the study, a Phase 3 randomized study cohort described in this posting, and an open label Phase 2 cohort described in NCT04693637, which has completed enrollment. In this Phase 3 part, approximately 302 eligible allogeneic HCT recipients will be enrolled and will receive 7 doses of posoleucel or placebo over 12 weeks, followed by a 12 week follow-up period.

Official Title
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Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ALVR105 Posoleucel (ALVR105,Viralym-M) Compared to Placebo for the Prevention of AdV, BKV, CMV, EBV, HHV-6, and JCV Infection and/or Disease, in High-Risk Patients After Allogeneic Hematopoietic Cell Transplant

Conditions
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Adenovirus Infection, BK Virus Infection, Cytomegalovirus Infections, Epstein-Barr Virus Infections, Human Herpes Virus-6 Infection, JC Virus Infection

Intervention / Treatment
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* Biological: Posoleucel (ALVR105)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Any age at the day of screening visit. No known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV Within 25 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment at time of dosing Meet one or more of the following criteria at the time of randomization: Related (sibling) donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B or -DR Haploidentical donor Matched or Mismatched unrelated donor Use of umbilical cord blood as stem cell source Ex vivo graft manipulation resulting in T cell depletion Received anti-thymocyte globulin or alemtuzumab (Campath-1H) Key Exclusion Criteria: History of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization Evidence of active Grade >2 acute GVHD Presence of non-minor uncontrolled or progressive bacterial, viral or fungal infections Known history or current (suspected) diagnosis of Grade ≥3 CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >1.0 mg/kg/day) within 24 hours prior to dosing Relapse of primary malignancy other than minimal residual disease Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Posoleucel (ALVR105)<br>Administered as 2-4 milliliter infusion, visually identical to placebo | Biological: Posoleucel (ALVR105)<br>* Administered as 2-4 milliliter infusion, visually identical to placebo<br>* Other names: Viralym-M;|
| Placebo Comparator: Placebo<br>Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105) | Biological: Placebo<br>* Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of clinically significant infections or episodes of end-organ disease |  | Through Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of clinically significant infections or episodes of end-organ disease |  | Through Week 26 | 
| Number of clinically significant infections or episodes of end-organ disease due to each virus |  | Through Week 14 and 25 | 
| Incidence of Adverse Events |  | Through Week 26 | 
| Overall and Non-Relapse Mortality |  | Through Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALVR105, Allogeneic Hematopoietic Cell Transplant, Posoleucel, Viralym-M, Virus-specific T cells (VSTs), Cytotoxic T Lymphocytes (CTLs)