Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Rare Diseases

Leukemia

Lymphoma

Cardiotoxicity

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Lymphosarcoma

Marielle Scherrer-Crosbie, MD, PhD

This is an observational study aiming to prospectively define the rate of occurrence, natural history and progression of cardiac dysfunction in adults, and to identify the patients at high risk of developing cardiovascular events. The study enrolls patients prior to infusion with CART cell therapy and follows them with serial echocardiography, cardiac biomarkers, clinical data, and quality of life questionnaire.

Patients have echo, blood draw, and QoL survey prior to CART infusion, then 2 days, 1 week, 1 month and 6 months following CART infusion. If patients experiences CRS, study team acquires echo within 72 hours of onset. As part of an optional substudy, patients wear an event monitor for 10 days, starting day of CART infusion.

Cardiovascular Effects of CART Cell Therapy

Cardiovascular Effects of Chimeric Antigen Receptor T-Cell (CART Cell) Therapy: An Observational Prospective Study

LV dysfunction, defined as a decrease in LV ejection fraction of at least 10% to less than or equal to 53%

Cardiovascular events are defined as hospitalization for symptomatic congestive heart disease, nonfatal acute coronary syndrome, cardiovascular death, nonfatal stroke, and all-cause mortality

Abramson Cancer Center at Penn Medicine

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Communicable Diseases

Lymphoma, Large B-Cell, Diffuse

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Acquired Immunodeficiency Syndrome

HIV Infections

Lymphoma, Follicular

Lymphoma, B-Cell

Lymphoma, AIDS-Related

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

B-cell Lymphoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Follicular Lymphoma

Acute Graft Versus Host Disease

Lymphoma AIDS Related

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	Eligibility	Organization
Cardiovascular Effects of CART Cell Therapy	NCT04026737	Leukemia Lymphoma Cardiotoxicity Risk Factor, Ca... Immunotherapy	18 Years -	Abramson Cancer Center at Penn Medicine
Cardiovascular Effects of CART Cell Therapy	NCT04026737	Leukemia Lymphoma Cardiotoxicity Risk Factor, Ca... Immunotherapy	18 Years -	Abramson Cancer Center at Penn Medicine
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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