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

Cytomegalovirus Infections Clinical Trial

— Prevent  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04693637
• Other study ID #: P-105-202 Phase 2
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 15, 2021
• Est. completion date: January 19, 2023

Study information

• Verified date: May 2024
• Source: AlloVir
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 19, 2023
• Est. primary completion date: January 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus Infection
• BK Virus Infection
• Communicable Diseases
• Cytomegalovirus Infections
• Epstein-Barr Virus Infections
• Human Herpes Virus-6 Infection
• Infections
• JC Virus Infection
• Virus Diseases

Intervention

Biological:
• Posoleucel (ALVR105)
Administered as 2-4 milliliter infusion

Locations

Country	Name	City	State
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Virginia	Charlottesville	Virginia
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Children's Mercy Kansas City	Kansas City	Missouri
United States	University of Minnesota	Minneapolis	Minnesota
United States	Weill Cornell Medical College	New York	New York
United States	Childrens National Medical Center	Northwest Rectangle	District of Columbia
United States	University of California, San Francisco Medical Center	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stony Brook University Hospital Cancer Center	Stony Brook	New York
United States	University of Kansas Hospital	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AlloVir

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. No abstract available. — View 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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV through Week 14	Through Week 14
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV through Week 26.	Through Week 26
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Adenovirus (AdV)	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).	Through Week 26
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to BKV	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 14 and Week 26 (6 endpoints each at Week 14 and Week 26).	Through Week 26
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Cytomegalovirus (CMV)	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).	Through Week 26
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Epstein-Barr Virus (EBV)	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).	through Week 26
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Human Herpes Virus 6 (HHV-6)	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).	Through Week 26
Secondary	Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to John Cunningham Virus (JCV)	The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).	Through Week 26
Secondary	Rates of Overall and Non-Relapse Mortality	The number of mortality events due to non-relapse causes through Week 52.	Through Week 52