Infections

All Conditions

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Occupational Diseases

Rare Diseases

Communicable Diseases

Cytomegalovirus Infections

COVID-19

Virus Diseases

Adenoviridae Infections

Laboratory Infection

Disease Attributes

Pneumonia

Pneumonia, Viral

Respiratory Tract Infections

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

DNA Virus Infections

Herpesviridae Infections

Cytomegalic Inclusion Disease

All Drugs and Chemicals

Glucocorticoids

Patients receive virus-specific CTLs intravenously (IV) over 30 minutes. Patients with partial response, stable disease, or progressive disease may receive up to 8 additional infusions of virus-specific CTL at least 2 weeks between each infusion.

Virus-specific Cytotoxic T-lymphocytes

May Daher, MD

This phase I trial tests the feasibility and safety of genetically modified cytotoxic T-lymphocytes in controlling infections caused by adenovirus (ADV), BK virus (BKV), cytomegalovirus (CMV), JC virus (JCV), or COVID-19 in immunocompromised patients with cancer. Viral infections are a leading cause of morbidity and mortality after hematopoietic stem cell transplantation, and therapeutic options for these infections are often complicated by associated toxicities. Genetically modified cytotoxic T-lymphocytes (CTLs) are designed to kill a specific virus that can cause infections. Depending on which virus a patient is infected with (ADV, BKV, CMV, JCV, or COVID-19), the CTLs will be designed to specifically attack that virus. Giving genetically modified CTLs may help to control the infection.

PRIMARY OBJECTIVE:

I. To assess the feasibility and safety of administering genetically engineered glucocorticoid receptor knock out virus specific cytotoxic T-lymphocyte (CTL) lines in immunosuppressed cancer patients with viral infections (BKV, JCV, CMV, adenovirus, COVID19).

SECONDARY OBJECTIVES:

I. To obtain preliminary data about the efficacy of administering genetically engineered glucocorticoid receptor knock out virus specific CTL lines in immunosuppressed cancer patients with viral infections (BKV, JCV, CMV, adenovirus, COVID19).

II. To assess the persistence of the administered cells in the patients. III. To obtain data about relapse free survival (RFS) and overall survival (OS).

OUTLINE:

Patients receive virus-specific CTLs intravenously (IV) over 30 minutes. Patients with partial response, stable disease, or progressive disease may receive up to 8 additional infusions of virus-specific CTL at least 2 weeks between each infusion.

After completion of study treatment, patients are followed up yearly for 15 years.

Study Assessing the Feasibility, Safety and Efficacy of Genetically Engineered Glucocorticoid Receptor Knock Out Virus Specific CTL Lines for Viral Infections in Immunosuppressed Cancer Patients

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Neoplasms

Nervous System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Syndrome

Carcinoma

Encephalitis

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Carcinoma, Merkel Cell

Encephalitis, Viral

Polyomavirus Infections

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

Slow Virus Diseases

Genital Diseases

Urogenital Diseases

Brain Diseases

Central Nervous System Diseases

Neuroinflammatory Diseases

Tumor Virus Infections

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Viral Diseases

Central Nervous System Infections

Infectious Encephalitis

Merkel Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Patients receive allogeneic BK-specific cytotoxic T-lymphocytes IV over 30 minutes. Patients achieving partial response, stable disease, or progressive disease are eligible for 19 additional infusions of CTL occurring at least 2 weeks after the previous CTL infusion if they meet the eligibility criteria for subsequent therapy.

Allogeneic BK-specific Cytotoxic T-lymphocytes

Laboratory Biomarker Analysis

Amanda L. Olson, MD

Amanda Olson

This phase II trial studies how well donor cytotoxic T lymphocytes work in treating patients with malignancies with BK and/or JC virus. Cytotoxic T lymphocytes are made from donated blood cells that are grown in the laboratory and are designed to kill viruses that can cause infections in transplant patients and may be an effective treatment in patients with malignancies with BK and/or JC virus.

PRIMARY OBJECTIVE:

I. To assess the efficacy, feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched BK specific cytotoxic T lymphocyte (CTL) lines (BK-CTLs) generated by ex vivo expansion to mediate antiviral activity in patients with any type of malignancies, and/or human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDs), and/or history of solid organ transplant with BK and JC infections.

SECONDARY OBJECTIVE:

I. To assess the persistence of the administered BK-CTLs generated by ex vivo expansion in patients with any type of malignancies, and/or HIV/AIDs, and/or history of solid organ transplant with BK and JC infections.

OUTLINE:

Patients receive allogeneic BK-specific cytotoxic T-lymphocytes intravenously (IV) over 30 minutes. Patients achieving partial response, stable disease, or progressive disease are eligible for 7 additional infusions of CTL occurring at least 2 weeks after the previous CTL infusion if they meet the eligibility criteria for subsequent therapy.

After completion of study treatment, patients are followed up periodically for 12 months.

Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus

Phase II Study Assessing the Effect of BK Specific CTL Lines Generated by Ex Vivo Expansion in Patients With BK Virus Infection and JC Virus Infection

The method of Thall et al will be used to monitor the probabilities of response.

The method of Thall et al will be used to monitor the probabilities of grade 3 or 4 GVHD.

Each outcome will be evaluated by tabulation and by fitting a Bayesian statistical regression model for binary outcomes as a function of covar. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.

Skin and Connective Tissue Diseases

Herpes Simplex

Epstein-Barr Virus Infections

Administered as 2-4 milliliter infusion, visually identical to placebo

Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)

Posoleucel (ALVR105)

Placebo

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.

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.

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

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

The average number of clinically significant infections or episodes of end-organ disease per participant due to Adenovirus (AdV), BK virus (BKV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human herpes virus 6 (HHV-6), or JC virus (JCV).

The number of clinically significant infections or episodes of end-organ disease per participant due to AdV, BKV, CMV, EBV, HHV-6, or JCV.

The number of participants with clinically significant infections or episodes of end-organ disease due to each of the following viruses: AdV, BKV, CMV, EBV, HHV-6, or JCV.

AlloVir

Adverse events are reported for the Safety Population which included all participants who received at least one dose of posoleucel or placebo.

Participants received posoleucel administered as 2-4 mL IV infusion once every 14 days for 7 doses.

Participants received placebo administered as a 2-4 mL IV infusion once every 14 days for 7 doses.

Participants received placebo administered as 2-4 mL IV infusion once every 14 days for 7 doses.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaskan Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Unknown

Race/Ethnicity, Customized

Safety Population: included all participants who received at least one dose of posoleucel or placebo.

The Sponsor decided to discontinue the Phase 3 part of the trial on 22 Dec 2023 following a pre-planned DSMB futility analysis concluding the study was unlikely to meet its primary endpoint; no safety concerns were identified. Data was not collected for efficacy analyses at Week 26 as planned. Participants were monitored through Week 26 for safety analyses.

Kevin Anderson

Includes modified Intent-to-Treat (mITT) Population comprised of all randomized participants who received study drug and completed through Week 14 visit.

Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 14

Data not collected due to early termination after DSMB futility analysis concluded the study was unlikely to meet its primary endpoint.

Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 26

HHV-6

Includes mITT Population comprised of all randomized participants who received study drug and completed through Week 14 visit.

Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus

Participants received posoleucel administered as 2-4 mL intravenous (IV) infusion once every 14 days for 7 doses.

Overall Study

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.

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.

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

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

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

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.

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).

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).

The number of mortality events due to non-relapse causes through Week 52.

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

Age, Categorical

Race (NIH/OMB)

United States

Region of Enrollment

Underlying Disease

Type of Transplant

Analysis Population will include all patients who received posoleucel.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Assessing the Feasibility, Safety and Efficacy of Genetically Engineered Glucocorticoid Receptor Knock Out Virus Specific CTL Lines for Viral Infections in Immunosuppressed Cancer Patients	NCT05101213	Adenovirus Infe... BK Virus Infect... Cytomegaloviral... Hematopoietic a... JC Virus Infect... Malignant Solid... Symptomatic COV...	Virus-specific ...	18 Years -	M.D. Anderson Cancer Center
Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus	NCT02479698	Acquired Immuno... BK Virus Infect... Human Immunodef... JC Virus Infect... Malignant Neopl... Merkel Cell Car... Merkel Cell Pol... Viral Encephali...	Allogeneic BK-s... Laboratory Biom...	-	M.D. Anderson Cancer Center
Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant	NCT05305040	Adenovirus Infe... BK Virus Infect... Cytomegalovirus... Epstein-Barr Vi... Human Herpes Vi... JC Virus Infect...	Posoleucel (ALV... Placebo	-	AlloVir
Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant	NCT05305040	Adenovirus Infe... BK Virus Infect... Cytomegalovirus... Epstein-Barr Vi... Human Herpes Vi... JC Virus Infect...	Posoleucel (ALV... Placebo	-	AlloVir
Study Assessing the Feasibility, Safety and Efficacy of Genetically Engineered Glucocorticoid Receptor Knock Out Virus Specific CTL Lines for Viral Infections in Immunosuppressed Cancer Patients	NCT05101213	Adenovirus Infe... BK Virus Infect... Cytomegaloviral... Hematopoietic a... JC Virus Infect... Malignant Solid... Symptomatic COV...	Virus-specific ...	18 Years -	M.D. Anderson Cancer Center
Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant	NCT04693637	Adenovirus Infe... BK Virus Infect... Cytomegalovirus... Epstein-Barr Vi... Human Herpes Vi... JC Virus Infect...	Posoleucel (ALV...	1 Year -	AlloVir

Spots Global Cancer Trial Database for jc virus infection