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Antiviral Agents

The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy.

Patients will receive partially HLA-matched VSTs as a single infusion. Patients who have a partial response (\>1 log decrease in viral load without clearance) or no response and do not have treatment-related dose-limiting toxicities are eligible to receive up to 3 additional doses from day 30 after the initial infusion and at 2 weekly intervals thereafter. The viral load of the virus (or viruses) that patients are initially treated for are monitored by viral PCR.

Virus Specific T-cell (VST) infusion

Michael Pulsipher, MD

Michael Keller, MD

The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.

The primary purpose of the study is to evaluate whether most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus.

Reconstitution of anti-viral immunity by donor-derived VSTs has shown promise in preventing and treating infections associated with CMV, EBV and adenovirus post-transplant. However, the time required to prepare patient-specific products and lack of virus-specific memory T cells in cord blood and seronegative donors, limits their value. An alternative is to use banked partially HLA-matched allogeneic VSTs. A prior phase II study at Baylor College of Medicine using trivirus-specific VSTs generated using monocytes and EBV-transformed B cells gene-modified with a clinical grade adenoviral vector expressing CMV-pp65 to activate and expand specific T cells showed the feasibility, safety and activity of this approach for the treatment of refractory CMV, EBV and Adenovirus infections. More recent protocols utilizing synthetic viral peptide pools allow ex vivo expansion of T-cells targeting multiple viral antigens in 10-12 days without use of viral transduction.

The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy.

This study will evaluate safety and efficacy of partially-matched VST therapy in A) patients who have persistent viral infections in the post-HSCT period, and B) patients with primary immunodeficiency conditions who have persistent viral infections and have not undergone HSCT.

The study agent will be assessed for safety and antiviral activity.

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation (ACES) PBMTC SUP1701

Feasibility will be defined as the ability of the investigators to identify suitable partially HLA- matched VST products from the VST bank at Children's National Medical Center for referred study subjects. The percentage of referred patients with potential partially-matched VST products identified will be recorded, as will timing between patient referral and treatment.

The safety endpoint, dose-limiting toxicity (DLT), will be defined as acute GvHD grades III-IV or grades 3-5 infusion-related adverse events or grades 4-5 non-hematological adverse events related to the T cell product within 30 days of each VST dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.

Peripheral blood and, where relevant, stool and urine will be monitored for CMV, EBV, and/or adenovirus viral load. For patients with multiple viral infections, the response against the primary viral target will determine the classification. For the infection under treatment response in viral load will be assessed at 30 days after the first VST infusion

Patient serum and peripheral blood mononuclear cells will be monitored for virus-specific activity during the 3 months following VST infusion by the following measures:

1. T cell phenotyping by flow cytometry (including % CD3, CD4, CD8, TCRalpha/beta and CD45RA-/CCR7+, among other markers)
2. Antiviral T cell responses to CMV, EBV, and/or Adenovirus antigens by IGN-g ELIspot (spot forming units) and Intracellular cytokine staining ( %IFN-gamma and TFNa+ of CD4 and CD8 cells)
3. T cell repertoire and antiviral specificity by TCR sequencing (%clonotype frequencies)

Persistence of infused T cells will be monitored at 1 month and 3 months following VST infusion using deep sequencing and additional tests as indicated to track the TCR v-beta repertoire in the patient peripheral blood prior to and post-infusion.

If a patient has organ involvement, clinical response will be monitored. For patients with EBV lymphoma and measurable disease, response will be assessed by RECIST criteria.

Overall survival at 6 and 12 months post VST infusion will be computed.

Principal Investigator

Subjects will receive Multivirus specific T cells on one of the following dose levels:

Level One: 5 x 10\^6 rCTLs/m2

Level Two: 1 x 10\^7 rCTLs/m2

Level Three: 2 x 10\^7 rCTLs/m2

Level Four: 5 x 10\^7 rCTLs/m2

If a patient has a partial response (as defined by a 50% fall in viral load) or receives medication (such as steroids) which may affect the persistence or function of the infused CTL they are eligible to receive up to 2 additional doses at the same initial dose. The minimum time between additional doses is 28 days.

Multi-virus Specific T cells

Helen E Heslop, MD

Patient's on this protocol have a type of blood cell cancer, other blood disease or a genetic disease and have received a stem cell transplant. The donor of the stem cells was either a brother or sister, another relative, or a closely matched unrelated donor. The patient is being asked to participate in this study which tests if blood cells from the donor that have been grown in a special way, can prevent or be an effective treatment for early infection by three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) and adenovirus.

Adenovirus is a virus that usually causes symptoms of a common cold, but can cause serious life-threatening infections in patients who have weak immune systems. It can affect the lungs and cause very serious pneumonia, and can also damage the gut, liver, pancreas and eyes.CMV can also cause serious infections in patients with weak or suppressed immune systems. It usually affects the lungs, causing a very serious pneumonia, but it can also affect the gut, the liver and the eyes. Approximately 2/3 of normal people harbor this virus in their body. In healthy people CMV rarely causes any problems because the immune system can keep it under control, but after a transplant, the risk of developing CMV disease is much higher because the immune system is so weak. EBV is the virus that causes glandular fever. It is also a life long infection like CMV that is normally controlled by the immune system. When immunity is weak, the virus can become active and cause fevers, enlarged lymph nodes and sometimes a type of cancer called lymphoma.

Investigators want to see if a kind of white blood cell called T lymphocytes (T cells)can be used to prevent and treat adenovirus, CMV and EBV in the early stages of reactivation or infection. T cells have been grown from the patient's stem cell donor in the laboratory in a way that will train them to recognize the virus and control it when they are given after a transplant. This treatment with specially trained T cells (also called CTLs) has had activity against these viruses in previous studies and in this study investigators want to see if they still have activity when they are made in a simpler and faster way. These donor-derived multivirus-specific special cell lines are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to evaluate whether donor-derived multivirus-specific special cell lines are safe and can control three viruses: EBV, CMV and adenovirus.

Blood has been previously taken from the patient and the donor to make the cells.

To make the special cell line, special blood cells called dendritic cells (DCs)were made first from the donor blood. Then, a specially produced gene called a plasmid that carries the adenovirus, CMV, and EBV genes was introduced into the dendritic cells. Dendritic cells with these new genes are then mixed with T cells to stimulate them. This stimulation trains the donor T cells to kill cells that are infected with CMV, EBV, and adenovirus. Once a sufficient numbers of T cells were made, they were tested to make sure they killed the patient's cells infected with these viruses, but not the patient's normal cells, and were frozen.

If the donor has never been infected with CMV, the CTLs made for the patient may not have activity against a CMV infection. If these donor CTLs show no activity against CMV infection, the cells will not be given.

The patient may receive Benadryl (diphenhydramine) and Tylenol (acetaminophen). Then, the donor's special cells will be thawed and injected into the patient's intravenous line. After the patient receives the cells, the levels of these three viruses in the patient's blood will be monitored. Investigators will also take blood to see how long the T cells given to the patient are lasting in the patient's body.

If the special cell infusion has helped the infection or if the patient has had a treatment (for example with steroid drugs) that might have destroyed the T cells that were given to them, then the patient is allowed to receive up to 2 more doses of the cells.

The patient will continue to be followed by his/her transplant doctors after the injection. The patient will either be seen in the clinic or contacted by a research nurse to follow up for this study every week for 6 weeks then at 8 weeks, and 3, 6, and 12 months. The patient may have other visits for standard care.

The patient will also have regular blood tests done to follow counts and the viral infection. To learn more about the way the T cells are working in the patient's body, up to an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at 1, 2, 4, 6, and 8 weeks and 3 months. Blood should come from the central intravenous line, and should not require extra needle sticks. Total time participation for this study will be 1 year.

Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes (VIRAGE)

Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes for the Prophylaxis and Treatment of EBV, CMV, and Adenovirus Infection Post Allogeneic Stem Cell Transplant (VIRAGE)

Safety and toxicity outcomes including DLTs, GvHD, clinical signs of viral infections, secondary graft failure and laboratory measurements will be summarized using descriptive statistics for each dose level (frequency table, means, standard deviations, medians and ranges).

Primary endpoint for the phase II portion of the study is antiviral efficacy, and is whether the institution of additional antiviral therapy post rCTL is needed.

The Methodist Hospital Research Institute

Center for Cell and Gene Therapy, Baylor College of Medicine

Baylor College of Medicine

Professor of Pediatrics-Hem-Onc Cell & Gene

Respiratory Tract (Lung and Bronchial) Diseases

Occupational Diseases

COVID-19

Laboratory Infection

Pneumonia

Pneumonia, Viral

Respiratory Tract Infections

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

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

If a patient has a partial response they are eligible to receive up to 4 additional doses at biweekly intervals. These doses would come from the original infused line if sufficient vials were available but may come from another line if there are insufficient cells in the original line.

Follow-up Assessments: The timing of follow-up visits is based on the date of CTL infusion. If a patient has multiple CTL doses the schedule resets again at the beginning so follow up relates to the last CTL dose.

Follow up will occur at 7 days, 14 days, 21 days, 28 days, 42 days, 90 days, 180 days, and 365 days post enrollment.

Trivirus Specific CTLs for EBV, CMV and Adenovirus Infection

Helen Heslop, MD

This trial is designed to evaluate the feasibility, safety and efficacy of most closely HLA-matched multivirus specific CTL lines (CHM-CTLs) in HSCT patients with EBV, CMV or adenovirus infections that are persistent despite standard therapy.

The primary objective of the study is to assess safety and feasibility of administering CTLs. Survival data will be collected by asking the transplant center to submit the routine Transplant Essential Data form that is sent to the Stem Cell Transplant Outcomes Database at 100 days and 1 year and includes data on survival status and other outcome measures.

Patients may be screened for study entry when they have persistent disease despite standard therapy as defined in the inclusion criteria. At that stage a search will be done of the available lines. Lines were generated from HSCT donors who consented to the use of CTLs not required for their recipient for research or from normal donors. All donors were screened and deemed to be eligible as transplant donors. We will also manufacture additional lines with the goal of covering common HLA types and will consult with the NMDP to determine what HLA types would be desirable. Additional donors will be screened by a transplant donor center physician and must be deemed eligible before a line can be manufactured.

CTL Lines: We will use trivirus specific CTL lines generated as described previously. Generation of trivirus-specific CTL lines requires the generation of several different components from PBMC. The CTL line will be derived from donor peripheral blood T cells, by multiple stimulations with antigen-presenting cells (APCs) presenting CMV, EBV and adenovirus antigens and expansion with interleukin-2 (IL-2). The APCs used to stimulate and expand the CMV-specific T cells will be derived from patient mononuclear cells and B lymphocytes.

To initiate the trivirus-specific CTL line, PBMC will be transduced with an adenovirus vector (Ad5f35-pp65) expressing the immunodominant antigen of CMV, pp65. The monocyte fraction of PBMC expressed and presented CMV-pp65 peptide epitopes to the CMV-specific T cell fraction of the PBMC, while the virion proteins from the adenovirus vector were processed and presented to the adenovirus-specific T cell fraction.

To expand trivirus -specific T cells we used EBV-transformed B lymphoblastoid cell lines (EBV-LCLs) transduced with Ad5f35-pp65. This transduction allows the EBV-LCLs to present CMV-pp65 and adenovirus virion peptides to the T cells as well as endogenously expressed EBV antigens.

EBV-LCLs are derived from PBMC-B lymphocytes by infection with a clinical grade, laboratory strain of Epstein-Barr virus (EBV). About 5 x 10\^6 PBMC, or 5 to 10 mLs of blood is required to generate the EBV-LCL

At the end of the CTL culture period, the frequency of T cells specific for each virus were determined using tetramer reagents if available. To test the functional antigen specificity of the CTL we will use overlapping peptide libraries for pp65 and adenovirus hexon and autologous and allogeneic LCLs in Elispot assays and we will perform cytotoxicity assays using unmodified PHA blasts and LCLs untransduced or transduced with Adhexon and CMVpp65 pepmix OR LCL transduced with Ad5f35-null and Ad5f35-pp65. Some lines will have aliquots sent for further characterization to the NIH where Drs Melenhorst and Barrett are developing assays to predict alloreactivity where they examine virus antigen-specific T cells using an extensive panel of activated T cells as antigen presenting cells (T-APC). These lines will be labeled with component number only and will not have subject identifiers.

The CTL lines will also be checked for identity, phenotype and sterility, and cryopreserved prior to administration according to SOP. Release criteria for administering the CTL to patients include viability \>70%, negative culture for bacteria and fungi for at least 7 days, endotoxin testing less than or equal to 5EU/ml, negative result for Mycoplasma, \<2% CD19 positive B cells, \<2% CD14 positive monocytes (or \<2% CD83 positive cells if Dendritic cells were used as stimulators) and HLA identity.

No Matched CTL Line Available: If no matched line is available the patient will be registered so that the feasibility of the approach can be assessed and the eventual outcome will also be collected.

CTL Line Available but Patient Status Changes: Patients clinical course that changes between screening and infusion will not be given the CTL and will be followed for eventual outcome.

Survival data will be collected by asking the transplant center to submit the routine Transplant Essential Data form that is sent to the Stem Cell Transplant Outcomes Database at 100 days and 1 year and includes data on survival status and other outcome measures.

Criteria for Selection of CTL Line: In general the line matching at the highest number of HLA loci will be selected. Matching at the allele level will be preferred but antigen level will be accepted or HLA-A and HLA-B. However consideration will also be given to the type of infection and activity of the line against that virus. For example for a patient with adenovirus infection a line that matches at 2 loci but that has recognition of adenovirus mediated through those antigens would be preferable to a line matched at 3 loci but with no demonstrated activity against adenovirus. The protocol chair will discuss each case with the principal investigators at each center to determine the optimal CTL line for each patient. If more than one line matches and there are insufficient cells to cover additional infusions a second CTL line will be reserved in the event that additional infusions are warranted. Patients with a partial response are eligible to receive an additional dose.

Premedications: Patients will be premedicated with Benadryl 1mg/kg (max 50 mg) IV and Tylenol 10 mg/kg (max 650 mg) PO.

Patients will be monitored according to institutional standards for administration of blood products and at a minimum will be monitored according to below: • Patients should remain in the clinic for at least one hour • Patients should remain on continuous pulse oximetry for at least 30 minutes • Vital signs should be monitored at the end of infusion then at 30 and 60 minutes

Supportive Care: Patients will receive supportive care for acute or chronic toxicity, including blood components or antibiotics, and other intervention as appropriate.

If a patient has a partial response they are eligible to receive up to 4 additional doses at a minimum 2 week intervals and if they meet the eligibility criteria for subsequent lines. These doses would come from the original infused line if sufficient vials were available but may come from another line if there are insufficient cells in the original line.

Follow-up Assessments: The timing of follow-up visits is based on the date of CTL infusion. If a patient has multiple CTL doses the schedule resets again at the beginning so follow up relates to the last CTL dose.

Follow up will occur at 7 days, 14 days, 21 days, 28 days, 42 days, 90 days, 180 days, and 365 days (+/- 2 days up to Week 8, and +/- 14 days for Days 90, 120, and +/- 28 days for 6 and 12 months, post-enrollment..)

The following assessments are considered standard-of-care unless identified below by " \* ":

Pre-Infusion: 1. History and physical exam including height and weight 2. Viral loads for EBV, adenovirus, CMV 3. Biopsy disease site, if appropriate 4. Imaging studies, if appropriate 5. Complete acute GVHD staging and grading information including assessments of rash, diarrhea, nausea/vomiting, weight and liver function tests 6. CBC with differential, platelet count 7. Liver function tests (bilirubin, alkaline phosphatase, AST, ALT) plus creatinine 8. Tacrolimus/cyclosporine level 9. \* Samples for laboratory studies

Post-Infusion: 1. Viral loads for CMV, EBV, adenovirus weekly at 1, 2, 3, 4 and 6 weeks and 3, 6 and 12 months. 2. Complete acute GVHD staging and grading information including assessments of rash, diarrhea, nausea/vomiting, weight and liver function tests weekly until Day 45 3. Chronic GVHD evaluation (if present) 3, 6, 9, and 12 months 4. CBC with differential and platelet count at 1, 2, 3, 4, and 6 weeks. 5. Infusion related toxicities within 24 hours and toxicity evaluation weekly until Day 30 and acute GVHD until Day 45 6. Steroid dose weekly until Day 42, and 3, 6 and 9 months 7. \* Samples for laboratory studies on Days 0, 14, 28 and 90 8. Infections through Day 42 and at 3, 6 and 12 months

Ancillary laboratory studies will include: 1) Assessment of virus-specific immunity based on CTL levels as measured by ELISPOT assays or tetramer assays. 2) Persistence of infused T cells based on PCR for non-shared antigen

Reporting Patient Deaths: The Recipient Death Information must be entered into the web-based data entry system within 24 hours of knowledge of a patient's death. If the cause of death is unknown at that time, it need not be recorded at that time. However, once the cause of death is determined, the form must be updated.

Donor Evaluation: - Complete history and physical examination - CBC, platelets, differential - Total protein, albumin, total bilirubin, alkaline phosphatase, ALT, AST, - HIV-1 antibody, HIV-2 antibody, HIV NAT, HTLV-1/2 antibodies, HBsantigen, HBc antibody, HCV NAT, CMV antibody, RPR, West Nile virus NAT, and Chagas testing - ABO and Rh typing - When the evaluation is complete, the Transplant Physician will note in the recipient's and donor's medical records that the tests have been evaluated, and the donor is acceptable.

Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)

Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation Or Infection With Adenovirus, CMV and EBV After Hemopoietic Stem Cell Transplantation (HSCT)

Brigham and Women's Hospital

Massachusetts General Hospital

National Marrow Donor Program

The Emmes Company, LLC

Duke University

Beth Israel Deaconess Medical Center

Children's Hospital Los Angeles

National Heart, Lung, and Blood Institute (NHLBI)

Boston Children's Hospital

University of Miami

Hackensack Meridian Health

University of California, Los Angeles

Skin and Connective Tissue Diseases

Herpes Simplex

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
Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation	NCT03475212	Cytomegalovirus... Adenovirus Infe... EBV Infection	Virus Specific ...	-	Children's Hospital Los Angeles
Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes (VIRAGE)	NCT01070797	Adenovirus Infe... Epstein-Barr Vi... Cytomegalovirus... Stem Cell Trans...	Multi-virus Spe...	-	Baylor College of Medicine
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
Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)	NCT00711035	Adenovirus Infe... EBV Infection	Trivirus Specif...	-	Baylor College of Medicine
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
Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)	NCT00711035	Adenovirus Infe... EBV Infection	Trivirus Specif...	-	Baylor College of Medicine

Spots Global Cancer Trial Database for adenovirus infection