Clinical trial NCT04693637: Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant
Official title: Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Adenovirus Infection
BK Virus Infection
Cytomegalovirus Infections
Epstein-Barr Virus Infections
Human Herpes Virus-6 Infection
JC Virus Infection
Keywords: Allogeneic Hematopoietic Cell Transplant
Posoleucel
ALVR105
Viralym-M
Lead sponsor: AlloVir
Sponsor class: INDUSTRY
First posted: 2021-01-05
Enrollment: 26
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This is a Phase 2 study to evaluate posoleucel (ALVR105, formerly 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: 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, an open label Phase 2 cohort described in this posting, and a randomized, placebo controlled Phase 3 cohort described in NCT05305040. In the Phase 2 part, 25 to 35 eligible allogeneic HCT recipients will be enrolled and will receive 7 doses of posoleucel over 12 weeks, followed by a 14 week follow-up period.

Eligibility criteria: Key Inclusion Criteria

* ≥1 year of age at the day of screening visit.
* Either no evidence of viral infection or viremia, or asymptomatic, viral infection with 3 or fewer viruses of interest at time of screening
* Within 15 and 42 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment
* 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
  * Unrelated donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B, -C, or -DR
  * Use of umbilical cord blood as stem cell source
  * Ex vivo graft manipulation resulting in T cell depletion
  * Lymphocyte Count \<180/mm3 and/or cluster of differentiation 4 (CD4) Count \<50/mm3

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 CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies
* Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose \>0.5 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.

Primary outcomes:
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease
timeFrame: Through Week 14
Secondary outcomes:
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease
timeFrame: Through Week 26
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Adenovirus (AdV)
timeFrame: Through Week 26
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to BKV
timeFrame: Through Week 26
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Cytomegalovirus (CMV)
timeFrame: Through Week 26
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Epstein-Barr Virus (EBV)
timeFrame: through Week 26
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Human Herpes Virus 6 (HHV-6)
timeFrame: Through Week 26
measure: Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to John Cunningham Virus (JCV)
timeFrame: Through Week 26
measure: Rates of Overall and Non-Relapse Mortality
timeFrame: Through Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Northwest Rectangle
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital Cancer Center
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
References:
citation: Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-HCT: Results from an Open-Label Cohort of a Phase 2 Trial Sanjeet S Dadwal, Michael Shuster, Gary Douglas Myers, Keith Boundy, Marshelle Warren, Elizabeth Stoner, Thuy Truong, Joshua A. Hill Blood (2021) 138 (Supplement 1): 1760.
citation: 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.
citation: Chandraker A, Regmi A, Gohh R, Sharma A, Woodle ES, Ansari MJ, Nair V, Chen LX, Alhamad T, Norman S, Cibrik D, Singh M, Alper A, Jain D, Zaky Z, Knechtle S, Sharfuddin A, Gupta G, Lonze BE, Young JH, Adey D, Faravardeh A, Dadhania DM, Rossi AP, Florescu D, Cardarelli F, Ma J, Gilmore S, Vasileiou S, Jindra PT, Wojciechowski D. Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. J Am Soc Nephrol. 2024 May 1;35(5):618-629. doi: 10.1681/ASN.0000000000000329. Epub 2024 Mar 12.