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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04693637
Other study ID # P-105-202 Phase 2
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
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
Health authority
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.

Study Design


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
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