Farydak

CAR-T cell therapy is an emerging treatment modality in relapsed and refractory multiple myeloma (MM). CAR-T therapy in MM relies on directing autologous T-cells to detect and clear myeloma cells expressing B-cell Maturation Antigen (BCMA). While BCMA CAR-T cell-treated patients achieve an excellent overall response rate, their response is often not durable. NT-I7 promotes CAR-T cell expansion and efficacy in pre-clinical lymphoma models. In patients receiving CD19-directed CAR-T therapy for lymphoma, NT-I7 augmented CAR-T expansion while being safe and tolerable. The impact of NT-I7 on BCMA CAR-T cells in multiple myeloma is unknown. This is a two-arm, double blind, placebo-controlled, randomized, single-site phase Ib study testing the safety and toxicity of adding NT-I7 to BCMA CAR-T therapy in patients with relapsed and refractory multiple myeloma. The hypothesis is that NT-I7 will promote CAR-T expansion and persistence which will enhance clearance of MM, while maintaining a favorable safety and toxicity profile. Patients receiving standard of care BCMA CAR-T (Cilta-cel) will be randomized to either NT-I7 or placebo. Correlative studies will evaluate CAR-T cell expansion, persistence, immune-phenotype, function and correlate with clinical outcomes.

The primary objectives of this study are to determine the safety of single agent Selinexor given with commercial bispecific antibody therapy in patients with Relapsed/Refractory Multiple Myeloma (RRMM) and to determine the MRD negativity rate at 10-5 at 12 months post bispecific antibody therapy. The investigators will enroll 27 patients with RRMM who are receiving commercial bispecific antibody therapy. Patients will be on treatment for 12 months or until disease progression, and will be followed for 24 months. Study assessments include completing a drug diary, having a safety check in call, and have history, clinical assessments, and labs taken. Twenty-seven patients will provide 80% power in a one-sample chi square test for a proportion assuming that the rate of negative MRD at 10-5 at 12 months post bispecific antibody therapy is 25% in historical control and 50% in the SEL+bispecific antibody experimental treatment group, under a one-sided 5% significance level.

The purpose of this study is to determine if UF-KURE-BCMA (B-Cell Maturation Antigen) chimeric antigen receptor T cells (CAR-T cells) can be used to treat relapsed or treatment refractory multiple myeloma (RRMM). This treatment uses T cells already present within the body that have been modified outside of the body by a virus and then returned by an infusion to fight cancer. The investigators are evaluating UF-KURE-BCMA because it uses a manufacturing process that is shorter than other Food and Drug Administration (FDA) approved CAR-T cells and only requires a simple blood draw. The standard treatments require weeks to manufacture the cells as well a special procedure to get an individual's cells. While the shorter manufacture time can be an advantage, the safety of this approach has not been demonstrated. The use of UF-KURE-BMCA is investigational and is not approved by the FDA outside of clinical trials. This is the first study of UF-KURE-BCMA in patients. Participants will give a pint of blood, which is the amount one would provide if they were to donate blood. The blood will be used to make the UF-KURE-BCMA cells. Participants will then receive chemotherapy followed by a one-time infusion of the experimental modified CAR-T cells. After this infusion, participants will be watched for side effects and follow up will continue for up to 15 years.

Patients with multiple myeloma experience a wide range of physical and psychological symptoms from the time of their diagnosis. Meanwhile, patients with aggressive lymphomas undergo unpredictable illness courses, resulting in goals of care conversations occurring late in the illness trajectory and aggressive care being received in the last 30 days of life. Early palliative care alongside usual cancer care has been shown to improve patient outcomes such as symptom burden, mood, and quality of life in patients with solid tumours (e.g. lung, breast or gynecological cancers), but has not been explored among patients with blood cancers to date. The goal of this clinical trial is to a brief early palliative care intervention for patients with multiple myeloma and aggressive B cell lymphoma and their caregivers (lymphoma only) attending the Princess Margaret Cancer Centre. The main goals of the study are: * To see if it is possible to apply the early palliative care intervention for patients with multiple myeloma and aggressive lymphoma and their caregivers (lymphoma only) * To see if this early palliative care intervention works well for these patients and caregivers * To compare patient and caregiver experiences with early palliative care and usual care * To explore perceptions and experiences of providing palliative care among healthcare providers involved in the care of these patients and caregivers. Patients, and their respective caregivers if participating, will be randomly assigned to one of two groups: one group will receive early palliative care in addition to usual care from their blood cancer doctor, and the other group will receive usual care from their blood cancer doctor only. All participants will be asked to fill out questionnaires about their quality of life, symptom burden, mood, and satisfaction with care throughout the study. Researchers will compare the results between the two groups to see if there are any improvements in quality of life for the patients who received early palliative care and their caregivers. Some patients and caregivers will be asked to take part in interviews at the end of the trial to answer questions about their experience taking part in the study. Some healthcare providers who care for these patients will also be asked to take part in interviews at the end of the trial to describe their perceptions and experiences of providing palliative care. The researchers will use the results of this study to guide in the development of a larger clinical trial.

A phase 2 study of venetoclax in combination with isatuximab and dexamethasone for relapsed/refractory multiple myeloma patients with t(11;14)