Clinical Trials

The purposes of this study are to analyze the ovarian function of female premenopausal melanoma survivors who have undergone immunotherapy, and compare with data from age-matched controls, prospectively investigate ovarian function in premenopausal women with melanoma undergoing immunotherapy, and to identify the impact of ovarian function change on the frequency and function of CD8+ T cells during immunotherapy.

Immunotherapy has revolutionized the therapeutic landscape for patients with metastatic RCC and response rates are higher than previously observed with tyrosine kinase inhibitors. Despite this, there is a growing need for molecular markers that can help identify patients who will benefit from immunotherapy, especially in the landscape of multiple available regimens, potential toxicities and financial burden. In this study, we propose to use blood biopsies to study tumor-derived extracellular vesicles (tdEVs) to assess disease burden, monitor response to therapy, and to predict earlier disease progression. In addition to tdEVs, these samples will also be analyzed for other biomarkers (circulating immune cells) to assess if they can be used to inform on tumor-immune cell interactions in real-time and potentially identify responders to immunotherapy.

The purpose of this study is to evaluate immune profile of Acute Myeloid Leukemia (AML) patients receiving Venetoclax plus Azacitidine induction chemotherapy.

The primary objectives for this study are: 

• The percentage of subjects who can enroll on an A2 CAR T-cell therapy study within approximately 6 months of documentation of HLA-A LOH status
• The percentage of subjects who can enroll on an A2 CAR T-cell therapy study within approximately 12 months of documentation of HLA-A LOH status
• The percentage of subjects who can enroll on an A2 CAR T-cell therapy study within approximately 18 months of documentation of HLA-A LOH status
• The percentage of subjects who can enroll on an A2 CAR T-cell therapy study within approximately 24 months of HLA-A LOH status
• Percentage of screened subjects experiencing loss of heterozygosity of HLA-A*02.

The purpose of this study is threefold:  the first aim is to use patient-derived fresh tumor tissue to create cell lines and 3D tumor models (i.e. organoids) that preserve the characteristics of the original tumor. The preservation of the original tumor's drug resistance/response profile will be a major focus of this aim. The second aim is to conduct high-throughput testing of various drugs (e.g., virotherapy, immunotherapy) on these cell lines and 3D tumor models. The completion of the second aim is an important step towards developing a platform that can help guide treatment decisions for future patients, based on the drug response observed in the cell lines and 3D tumor models. The third aim is to use pan-omics approaches (i.e., genomics, proteomics, metabolomics) to find markers of drug response based on the results of the high-throughput drug testing on the cell lines and 3D tumor models.

The purpose of this study is:

• To assess the efficacy of treatment with checkpoint inhibitors (Pembrolizumab or Nivolumab) in metastatic gastric and esophageal carcinoma through retrospective chart review.
• To explore if response to checkpoint inhibitors is dependent on biomarkers on tumor tissue.

The chimeric antigen receptor (CAR) T-cell therapy is a revolutionary cellular immunotherapy strategy that has transformed the treatment of B cell malignancies by engineering T cells to recognize B cell specific tumor markers; however, attempts to treat solid tumors with CAR T-cells have identified unique challenges that have rendered CAR T cells less effective against these tumors. Conventional CARs are designed to target tumor-associated antigens, but antigenic heterogeneity and the variable nature of surface antigen expression provide escape mechanisms for solid tumors from CAR T-cell attack. [1, 2] The solid tumor stroma acts as an immunosuppressive cloud that impedes the homing of peripheral CAR T-cells into the tumor microenvironment (TME). The hostile TME can also drive CAR T-cells to functional exhaustion and metabolic dysfunction, thus blunting the therapeutic efficacy of CAR T-cells.[3] Oncolytic viruses or radiation that generate local inflammation in the TME have been shown to promote T cell homing and infiltration [4] but do not address the exhaustion of tumor infiltrating lymphocytes (TILs). The PD-1/PD-L1 cascade allows tumors to evade the immune system by suppressing T cell function within the TME. [5, 6] An ideal adoptive cellular therapy must possess the ability to not only return to the site of the tumor but must also retain cytotoxic potential after a recognition event. We present here a CAR design that allows PD-1 to recognize PD-L1 on the tumor; however, the intracellular CAR design is one that results in T cell activation as opposed to inhibition. We hypothesize that targeting melanoma with a PD-1 (MC9324) CAR TIL therapy would capitalize on the tumor homing machinery of the TIL to drive the CAR TIL to the tumor where engagement of the PD-1 domain of the CAR with PD-L1 on the tumor cell would result in T cell cytotoxic killing.

The purpose of this study is to store blood, serum and bone marrow so that they can be used for laboratory studies that may contribute to finding the exact function of the CART cells or T-cell engager therapy such as bispecific and trispecific antibodies and the factors that may determine disease progression and treatment response.

Although survivorship recommendations have been developed in areas such as lymphoma and stem cell transplant, the long-term effects of CAR-T therapy are unknown. In addition, relatively little is known about the psychosocial impact of CAR-T on survivors and their caregivers. Due to the intensive nature of CAR-T treatment and its unique side effects, including neurotoxicity in the acute setting and infections and financial burden in the long-term setting, a longitudinal study that assesses these issues in a quantitative and qualitative fashion is required. Consideration of both patient and caregiver needs is important for the provision of appropriate and effective health services, particularly in intensive cancer treatments that require a caregiver, such as CAR-T.

Our objective in this proposal is to define the long-term needs of CAR-T survivors using patient-reported health-related quality of life (QOL) measures, qualitative interviews, and adverse event data. The rationale for our proposed study is that it will provide the necessary knowledge on CAR-T survivor physical, mental, and social health to formulate a CAR-T specific survivorship program that can be implemented and studied in the future.

We aim to recruit 100 subjects (50 survivors and 50 caregivers) to the study. Inclusion Criteria are the following:  age ≥ 18, blood cancer diagnosis (including B-ALL, multiple myeloma, and lymphoma), receiving a CAR-T product, able to complete a written questionnaire in English either independently or with assistance, and able to perform a verbal interview either in person or via phone teleconference. We will survey patients at baseline and then at pre-specified timepoints up to 2 years after CAR-T. Survey questionnaires that have been previously validated in cancer populations will be used to assess: overall quality of life, psychosocial impact, cognitive function, post-traumatic stress, spiritual well-being, and financial toxicity. Patient demographics, adverse events, and comorbidities will also be collected via survey and/or medical record review. A selected subset of participants (10 survivors and 10 caregivers) will be chosen to undergo semi-structured open ended interviewing to obtain a qualitative understanding of unmet needs, social support, and distress. Data will be analyzed and compared to historical lymphoma and transplant cohorts.