Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lymphoma

Acquired Immunodeficiency Syndrome

HIV Infections

Lymphoma, AIDS-Related

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Lymphoma AIDS Related

B-cell Lymphoma

HIV+ Participants that were treated with autologous hematopoietic stem cell transplant.

HST-NEETs are manufactured from an autologous peripheral blood or MNCs via apheresis collection and will be administered as a single intravenous (IV) infusion of 2x10\^7/m\^2 cells between 3 Days and 7 Days post-ASCT.

HST-NEETs

Day 0 is the day of bone marrow transplantation.

Bone Marrow Transplant

Christine Borchert

Nicole Ritzau

Matthew Mei

Anne Renteria

Marco Ruiz Andia

Alex Lazaryan

Lawrence Morris

Paul Rubinstein

Rich Ambinder

Uroosa Ibrahim

Anna A Alperovich

Parastoo Dahi

Stefan Barta

George Carrum

Uday Popat

Steve Devine, MD, MS

This is a Phase II multi-center trial single arm trial of autologous transplantation (ASCT) followed by administration of HST-NEETs for treatment of HIV associated lymphoma

Eligible participants will have 100-120 mL of peripheral blood or 80-100 mL of MNCs via apheresis collected and shipped to Children's National Hospital at ambient temperature. The sample will be used to manufacture the HST-NEET product. The autologous peripheral blood stem cell graft suitable for rescue following conditioning will be obtained either before or after the collection of blood to generate HST-NEETs. Pre-transplant conditioning will consist of BEAM; BCNU 300 mg/m\^2 on Day -6, Etoposide 100 mg/m\^2 BID and Ara-C 100 mg/m2 BID on Days -5, -4, -3 and -2 and Melphalan 140 mg/m2 on Day -1. ASCT on Day 0. If the mobilized graft contains greater than 5.0 x 106 CD34+ cells per kg, any additional cells should be cryopreserved as a "back-up" graft in the event of graft failure related to the HST-NEETs. Participants will receive one dose (2 x 107 cells/m\^2 ) of HST-NEETs between Days +3 to +7 based on the clinical condition of the participant. If this window is missed, the HST-NEETs may be administered up to Day +30 post-ASCT. Participants will be followed for at least one year after ASCT.

HIV Antigen-specific T-cells Targeting Conserved Epitopes (HST-NEETs) BMTCTN1903

Administration of HIV-specific T Cells to HIV+ Patients Receiving High Dose Chemotherapy Followed by Autologous Stem Cell Rescue - Auto -RESIST BMT CTN 1903

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

CR or PR will be assessed according to the LYRIC criteria

Overall survival is defined as death from any cause

Time to neutrophil recovery will be the first of three consecutive labs of greater than or equal to 500 neutrophils/μL following the expected nadir. Time to platelet engraftment will be the date platelet count is greater than or equal to 20,000/μL for the first of three consecutive labs with no platelet transfusions 7 days prior.

The incidence of viral, fungal and bacterial infections will be tabulated. All Grade 2 and Grade 3 infections will be reported according to the BMT CTN Technical MOP from Day 0 up to 1 year post-transplant. Infections of interest will be captured and described. The incidence rate of infections is defined by the number of infections divided by the total person-time accumulated over the duration of the study.

Non-Relapse Mortality (NRM) is defined as death occurring in a participant without relapse progression and will be measured at 6 months and at 1 year.

Toxicities related to the BEAM conditioning regimen and HST-NEETs infusion beyond the 24 hour acute toxicity monitoring period will be defined by using the version 5.0 CTCAE criteria. All grades of toxicity related to HST-NEETs will be collected. Only grade 3 or higher conditioning regimen related toxicities will be collected.

Blood specimens will be collected prior to the initiation of conditioning, and at Days 100, 6 months and 1 year post-ASCT. The presence of clonal Ig DNA in plasma will be assessed at each of these time points.

Impact on intact proviral reservoir assessed using the IPDA Day 100 post-ASCT as compared to baseline at 4-8 weeks prior to transplant.

HIV RNA in plasma will be measured by a sensitive investigational single copy assay (SCA, detection limit 0.38 copy/ml). Blood specimens will be collected, and plasma HIV RNA measured, at study visits corresponding to those associated with IPDA testing: 4-8 weeks prior to transplant, and at Days 100, 6 months and 1 year post-ASCT.

This assay will be measured at study visits corresponding to those associated with IPDA testing: 4-8 weeks prior to transplant, and at Days 100, 6 months and 1 year post-ASCT. This assay will provide information about the proviral reservoir in patients where the IPDA fails due to sequence variation.

Persistence and expansion of HST-NEETs will be measured by frequency of HIV-1 antigen-specific (gag, pol, nef) CD8+ T-cells by ELIspot at baseline and post-infusion at timepoints at Day 100, 6 months, and 1 year post transplant. Change in T cell responses from baseline to post-infusion, measured by frequency of cells secreting IFN-γ by multimer analysis and/or intracellular cytokine staining and/or ELIspot and/or TCR sequencing will be done depending on PBMC cell numbers available and reagent availability.

Feasibility is defined as a participant receiving HST-NEETs within 1 week post-ASCT; Efficacy will be measured by the reduction in intact proviral reservoir.

Participants are considered a failure for this endpoint if they die or if they relapse/progress or receive anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (greater than 3cm)

Acute infusion related toxicities are defined as toxicities related to the infusion of HST-NEETs that occur within 24 hours of the infusion.

Impact on intact proviral reservoir will be assessed using the IPDA at 4-8 weeks prior to transplant and 12 months following ASCT

National Heart, Lung, and Blood Institute (NHLBI)

Blood and Marrow Transplant Clinical Trials Network

National Cancer Institute (NCI)

National Marrow Donor Program

Children's National Research Institute

Catherine Bollard

Primary Investigator

Primary Central Nervous System Lymphoma

Approximately six (6) subjects will be treated to determine the RP2D. At the designated RP2D, approximately fifteen (15) additional subjects will be treated.

EB103 is an autologous T-cell therapy whereby a subject's own T cells are transduced with a lentiviral vector expressing the EB103 transgene.

EB103

Teresa Klask

Pei Wang, PhD

This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of an autologous T-cell therapy (EB103) and to determine the Recommended Phase II Dose (RP2D) in adult subjects (≥ 18 years of age) who have relapsed/refractory (R/R) B-cell NHL. The study will include a dose escalation phase followed by an expansion phase.

This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of EB103 and determine the RP2D in adult subjects (≥ 18 years of age) who have R/R B-cell NHL.

The study will include a dose escalation phase followed by an expansion phase. A traditional dose escalation model (3+3 design) will be used to determine the RP2D, and once determined, the expansion phase will commence. Additional subjects will be enrolled in the expansion phase to further confirm the safety profile of EB103 at the RP2D and evaluate the preliminary efficacy of EB103.

T-Cell Therapy (EB103) in Adults With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)

An Open-Label, Dose Escalation, Multi-Center Phase I/II Clinical Trial of EB103 T-Cell Therapy in Adults With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (NHL)

The incidence of Dose Limiting Toxicities (DLTs) that occur within 28 days following EB103 T-cell infusion will be assessed. A DLT consists of any adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, concomitant medication, or intercurrent illness that occurs within 28 days following EB103 T-cell infusion and meets specified criteria as outline in the clinical protocol. The type, frequency, and severity of each DLT, AE, and abnormal laboratory value will be documented to assess the safety and tolerability of EB103.

The type, frequency, and severity of Treatment-Emergent Adverse Events (TEAEs) will be assessed and includes an AE that starts any time from initiation of EB103 administration through and including 90 days after EB103 administration.

Listing and summaries will be prepared for the following type of events: TEAEs, SAEs, Grade 3 or higher AEs, treatment related AEs (conditioning chemotherapy, protocol-mandated procedures, or EB103), and AEs leading to death. AESIs, including but not limited to acute infusion reaction, CRS, ICANS, prolonged cytopenia, TLS, MAS/HLH, SPM, and hypogammaglobulinemia.

The type, frequency, and severity after Treatment-Emergent Laboratory Abnormalities will be assessed and includes a laboratory abnormality that, compared to baseline, worsens by at least one grade with 90 days after EB103 administration.

The RP2D will be determined by the study Dose Escalation Committee (DEC) and chosen based on the maximum tolerated dose (MTD) but will not exceed the MTD and the maximum administered dose (MAD). The RP2D will also be based on the manufacturing capability.

The Overall Response Rate (ORR), defined as the proportion of subjects with a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR) will be assessed.

The Disease Control Rate (DCR), defined as the proportion of subjects with BOR of either Complete Response (CR), Partial Response (PR), or Stable Disease (SD) will be assessed.

The Duration of Response (DOR), defined as the time from first response to Progressive Disease (PD) or death will be assessed.

The Progression-Free Survival (PFS), defined as the time from EB103 infusion to PD or death will be assessed.

The Event-Free Survival (EFS) will be defined as the time from EB103 T-cell infusion to the earliest of the following events: death from any cause, PD, or starting a new anticancer therapy.

The Overall Survival (OS) will be defined as the time from EB103 T-cell infusion to the date of death.

The peak exposure (Cmax) will be measured in our study subject population.

Time to reach peak exposure (Tmax) will be measured in our study subject population.

Partial area under the curve (pAUC) will be measured in our study subject population.

Eureka Therapeutics Inc.

Estrella Biopharma, Inc.

Symptoms and General Pathology

Leukemia

Communicable Diseases

Lymphoma, Large B-Cell, Diffuse

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Follicular

Hematologic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Follicular Lymphoma

Acute Graft Versus Host Disease

Clinical information on participants, who carry a diagnosis of HIV disease AND received CAR19 therapy outside of a clinical trial between August 30, 2017 and August 31, 2021 will be captured

This protocol will develop an observational cohort of PLWH who have been or are being treated with CAR19 therapy outside of an AMC clinical trial. Following regulatory approval of this protocol, sites will be asked to capture information of participants, who carry a diagnosis of HIV disease AND received CAR19 therapy outside of a clinical trial between August 30, 2017 and August 31, 2021. Data captured will include data points are available as part of standard of care for participants undergoing CAR19 therapy. AMC investigators, as well as non-AMC investigators will identify eligible participants to the CIBMTR, who in turn will provide the AMC statistical center with de-identified data

Two landmark trials have led to the FDA approval of two different CD19 directed chimeric antigen receptor (CAR) T cell (CAR19) products in the United States for the treatment of relapsed or refractory (RR) large B-cell lymphoma after two or more lines of systemic therapy: tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta ®). In the ZUMA-1 registration trial for axicabtagene ciloleucel (axi-cel), 42% of the 101 treated patients achieved a complete response (CR), and with a median follow up of 15 months, the projected 1year progression free survival (PFS) was 70%. In a recent updated analysis, the CR rate was 58% with about 40% of patients having durable remissions at 2 years of follow up. Similar results were seen in the JULIET registrational trial for tisagenlecleucel (tisa-cel) with an overall response rate (ORR) of 52%, and a CR rate of 40% in the 93 patients evaluable for response; with a median follow up of 14 months, the estimated 12-months relapse-free survival was 65% (79% among patients with a CR). Tisagenlecleucel is also approved for the treatment of acute B-lineage lymphoblastic leukemia in patients up to the age of 25 years. Unfortunately, in both trials patients with known HIV infection were excluded. Therefore, no safety or efficacy data for treatment with CAR19 in PLWH exists, and access for PLWH in the US to this potentially curative treatment has been limited.

This has to be contrasted with the fact that malignancies, and specifically lymphomas, remain a major contributor to early mortality in PLWH. With a lifetime risk of cancer ranging between 24-40%, the leading cause of death in PLWH in economically developed countries is cancer, and the most common cancer in PLWH in the US remains Non-Hodgkin lymphoma (NHL). While early during the HIV epidemic, outcomes for PLWH and aggressive B-cell lymphomas were significantly worse compared to immunocompetent patients, this is no longer the case for the majority of PLWH, owing mainly to effective antiretroviral therapies leading to better tolerance of myelosuppressive chemotherapy and a consequent paradigm shift in aggressive therapies for HIV-associated lymphoma. It has been repeatedly demonstrated that PLWH have been able to safely tolerate aggressive high-dose chemotherapy, as well as autologous and even allogeneic hematopoietic cell transplant.

Observational Study of People Living With HIV Treated With CD19-directed CAR T Cell

Observational Cohort Study of People Living With HIV Treated With CD19-directed CAR T Cell Therapy for B-cell Lymphoid Malignancies

Toxicities related to CAR19 therapy will be reported by Common Terminology for Adverse Events (CTCAE) criteria, as well as American Society for Transplantation and Cellular Therapy (ASTCT) criteria (for cytokine release syndrome)

CD4 count on day of leukapheresis, 3 months post CAR19 therapy, 6 months post CAR19 therapy, and 12-months post therapy will be measured

Absolute lymphocyte count on day of leukapheresis, 3 months post CAR19 therapy, 6 months post CAR19 therapy, and 12-months post therapy will be measured

HIV viral load on day of leukapheresis, 3 months post CAR19 therapy, 6 months post CAR19 therapy, and 12-months post therapy will be measured

Defined as complete remission plus partial remission

Defined as complete disappearance of all disease

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
HIV Antigen-specific T-cells Targeting Conserved Epitopes (HST-NEETs) BMTCTN1903	NCT04975698	HIV Associated ...	HST-NEETs Bone Marrow Tra...	15 Years -	National Heart, Lung, and Blood Institute (NHLBI)
HIV Antigen-specific T-cells Targeting Conserved Epitopes (HST-NEETs) BMTCTN1903	NCT04975698	HIV Associated ...	HST-NEETs Bone Marrow Tra...	15 Years -	National Heart, Lung, and Blood Institute (NHLBI)
T-Cell Therapy (EB103) in Adults With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)	NCT06343311	B-Cell Non-Hodg... Lymphoma, Non-H... Lymphomas Non-H... Non-Hodgkin Lym... Non-Hodgkin's L... Large B-Cell Ly... Lymphoma, Non-H... Lymphoma Refractory Non-... Relapsed Non-Ho... Lymphoma, Non-H... HIV Associated ... CNS Lymphoma High-grade B-ce... Refractory B-Ce...	EB103	18 Years -	Estrella Immunopharma, Inc.
Observational Study of People Living With HIV Treated With CD19-directed CAR T Cell	NCT05784415	Leukemia Leukemia, Lymph... Lymphoma, Large... Follicular Lymp... Lymphoma, B-Cel... Lymphoma, Folli... Lymphoma, Non-H... HIV Infections HIV Associated ... HIV Disease; Ly...		18 Years -	AIDS Malignancy Consortium

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