Sezary Syndrome

Researchers are studying the safety, how the body processes, and effectiveness of a drug called CHT101 in adults aged 18 to 70 who have certain types of relapsed or refractory blood cancers, including Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma, and Non-Hodgkin Lymphoma. This research is a Phase 1, open-label, single-arm study aiming to find the best dose and observe initial effects in these patients. The treatment involves giving CHT101, a CD70-targeted UCAR-T cell therapy, to participants. The study starts with a dose escalation phase where three dose levels will be tested. After a safety review committee evaluates safety, drug levels in the body, and early responses, a dose expansion phase will begin to further assess the treatment. Participants will be closely monitored for side effects, treatment responses, and how the drug moves and acts in the body over two years. Researchers will measure dose-limiting toxicity and maximum tolerated dose within 28 days of the first infusion. Other outcomes include adverse events, response rates, progression-free survival, overall survival, pharmacokinetics, and pharmacodynamics. Safety and effectiveness will be followed for up to two years after treatment begins.

Researchers are studying the use of unlicensed cryopreserved cord blood units (CBUs) for transplantation in both pediatric and adult patients with various blood-related cancers and other disorders affecting the blood-forming system. This observational study aims to evaluate outcomes such as the recovery of a certain level of white blood cells after transplantation, as well as the incidence of infections, infusion reactions, survival rates, and graft-versus-host disease over time. The study involves patients receiving unlicensed CBUs at multiple U.S. transplant centers. These CBUs are used for patients with hematologic malignancies and other blood disorders. The protocol collects data on patients who receive these unlicensed transplant units, without administering a new treatment but observing the outcomes after transplantation. Participants will be monitored for neutrophil recovery at 60 and 100 days post-transplant, along with assessments of infection transmission, infusion reactions, survival one year after transplant, and occurrences of acute and chronic graft-versus-host disease. Platelet engraftment levels will also be tracked. The study includes patients of any age and follows them through the transplantation and recovery process to gather information on these key outcomes.

Researchers are evaluating IM-1021, an antibody-drug conjugate, in participants with advanced cancers including B-cell lymphomas and solid tumors. This Phase 1 open-label study aims to assess the safety, tolerability, pharmacokinetics, and early anti-tumor effects of IM-1021. The study includes a dose escalation phase to find safe doses and schedules, followed by an expansion phase to further assess these doses in specific cancer types. IM-1021 is given intravenously on a 21-day cycle, starting at 2 mg/kg, with alternative dosing schedules possible. The study has two parts: Part A focuses on escalating doses to evaluate safety and determine recommended doses, while Part B expands treatment in groups with specific cancer types to further evaluate safety and preliminary activity. Participants will undergo regular safety assessments including monitoring for treatment-related side effects from the first dose through 37 days after the last dose. Researchers will also measure drug levels in the body and evaluate anti-tumor activity starting at week 6 until disease progression or study discontinuation. The total study duration varies per participant. Safety, tolerability, and pharmacokinetic data will guide future development of IM-1021.

Researchers are studying JV-213, a new type of autologous CAR T cell therapy targeting CD79b, in adults with relapsed or refractory B-cell lymphomas. This phase 1 trial aims to find the highest dose of JV-213 that can be safely given to patients who have not responded to previous treatments. The study also explores how well the treatment works and how it affects the body, including how the immune cells behave and potential biomarkers linked to response and side effects. Participants will receive JV-213 through an intravenous (IV) infusion after their own T cells are collected via leukapheresis. The trial has two parts: a dose escalation phase where small groups receive increasing doses to find the maximum tolerated dose, and a dose expansion phase where more participants receive the recommended dose identified in the first part. Each group includes 3 to 6 patients, and dosing is adjusted based on safety observations. During the study, participants will be monitored closely for side effects using standard criteria and evaluated for tumor response and symptom relief. Researchers will collect blood and tumor samples to study the treatment’s effects and track patient health over about one year. Safety, tumor response rates, duration of response, progression-free survival, and overall survival will be measured throughout the trial.

Researchers are evaluating PTX-100 monotherapy in adult patients with relapsed or refractory Cutaneous T-Cell Lymphoma (CTCL) to assess its efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD). This open-label, phase 2 randomized study includes patients with confirmed CTCL who have previously received at least two systemic therapies and have measurable disease. The purpose is to better understand how PTX-100 works and determine the optimal dosing for this patient group. PTX-100 will be given by intravenous infusion over 60 minutes on days 1 to 5 of each cycle. In the initial phase (Phase 2a), participants will be randomly assigned to receive either 500 mg/m2 or 1000 mg/m2 doses every 14 days for four cycles, followed by a 21-day cycle for up to 18 months. In the subsequent Phase 2b, 75 participants will receive the recommended optimal dose identified from Phase 2a following the same infusion schedule. Participants will undergo a 28-day screening period before treatment begins. During the study, safety blood tests will be collected on the first day of each cycle, and detailed blood samples will be taken during the first cycle to study how PTX-100 behaves in the body. Patients will also have skin evaluations, safety exams, and quality of life questionnaires at each cycle day 1 visit. The study will continue for up to 18 months or until disease progression, unacceptable side effects, or other reasons for stopping treatment arise.

Researchers are evaluating the safety and effectiveness of tofacitinib 2% cream for treating early-stage Cutaneous T-cell Lymphoma (CTCL) in adults diagnosed with stages IA, IB, or IIA. This phase 2 trial aims to assess how well the cream works on skin lesions and monitor side effects. The study also looks at itch relief, quality of life, and tumor biomarkers before and after treatment. Participants will apply a thin layer of tofacitinib 2% cream twice daily on up to five eligible skin lesions. The treatment phase lasts 12 weeks, with options to extend treatment for up to one year. Researchers will evaluate responses at multiple time points, including weeks 4, 8, 12, and beyond for those continuing treatment. During the study, participants will have regular assessments of their skin lesions using specialized scoring systems, report itch severity, and complete quality of life questionnaires. Safety and adverse events will be monitored throughout the study and up to one year. Tumor samples will be analyzed to understand the biological effects of the cream. Overall participation may last about one year depending on treatment extension.

Researchers are evaluating a gene therapy treatment for adults with certain mature T-cell lymphomas that express the CCR4 protein and have not responded to or have relapsed after previous treatments. This phase I trial aims to test the safety of giving participants their own white blood cells, modified to attack the CCR4 protein on their cancer cells. The study focuses on various T-cell lymphoma subtypes, including peripheral T-cell lymphoma and cutaneous T-cell lymphoma, among others. Participants will first undergo leukapheresis, a procedure to collect their T-cells, which will then be genetically modified to express anti-CCR4 chimeric antigen receptors (CARs). Before receiving the modified cells, participants will have conditioning chemotherapy with cyclophosphamide and fludarabine over three days. The modified CAR T cells will then be infused intravenously. The study includes dose escalation to find the maximum tolerated dose, with groups receiving varying doses, followed by an expansion cohort at the identified dose level. Throughout the trial, participants will undergo extensive monitoring including CT, PET, and MRI scans, biopsies, blood and urine tests, and heart and lung function assessments. Leukapheresis and cell infusions will be carefully timed, and participants will be followed for up to 15 years to assess long-term safety and treatment effects. Visits will include blood tests frequently during the first two years and yearly follow-ups thereafter, with some visits possibly conducted via telehealth.

Researchers are studying a new microdevice designed to release up to 19 different cancer drugs directly into skin lesions caused by cutaneous T cell lymphoma (CTCL) or peripheral T cell lymphoma (PTCL). This pilot and feasibility study aims to evaluate the safety of inserting and removing the microdevice within cancerous lesions and to assess how the device may help identify effective drugs for treating these lymphomas. The FDA has approved all the drugs used in the device, though not specifically for these lymphomas or the microdevice itself. Participants will have up to four microdevices placed percutaneously into two skin lesions, with two devices per lesion. Some patients will also receive standard systemic therapy as determined by their oncologist or dermatologist. Patients in the expansion cohort will receive this standard therapy while their clinical progress is followed. The microdevices release very small doses of drugs directly to the tumor tissue, and after removal, tumor response to the drugs will be analyzed. During the study, participants will undergo skin biopsies and laboratory tests before device placement. Researchers will monitor for any adverse events related to the microdevice over two years and will analyze the quality of tissue retrieved with the device. The study will also evaluate drug responses within the tumor and examine molecular markers using advanced genetic and histological methods over several years. Participation includes follow-ups to assess safety and tumor reactions, with the total follow-up lasting up to five years.

Researchers are collecting detailed information in a registry to better understand various types of mature T-cell and natural killer (NK)-cell lymphomas. This observational study aims to improve knowledge about these rare blood cancers by creating a comprehensive database that includes clinical information and tumor samples from participants. The study is sponsored by Memorial Sloan Kettering Cancer Center and focuses on multiple specific T-cell lymphoma subtypes as defined by recognized classification guidelines. Participants with confirmed mature T-cell or NK-cell lymphoma may choose to provide optional blood and nail samples for future research and biobanking. The study does not involve experimental treatments but gathers data prospectively from individuals meeting strict diagnostic criteria, including those receiving systemic therapy for certain cutaneous lymphoma types. This approach supports long-term data collection rather than testing new therapies. During the study, participants will have clinical data and tumor specimens collected and recorded. Researchers will track the number of participants contributing to the T-cell Lymphoma Master Repository over a 10-year period. The study involves ongoing follow-up to measure disease status and treatment response, with no direct intervention required. Participation helps build a resource to advance future research and understanding of these lymphomas.

Researchers are evaluating the safety of combining bexarotene with total skin electron beam (TSEB) radiotherapy in people with mycosis fungoides (MF), a common form of cutaneous T-cell lymphoma (CTCL). Bexarotene, a vitamin A derivative, activates proteins that may stop the growth of cancer cells, while TSEB radiotherapy treats the entire skin surface with low-dose radiation to kill cancer cells without affecting deeper tissues. The study aims to see if using both treatments together is more effective than using them separately or one after the other. Participants start with bexarotene taken orally daily at 150 mg, increasing to 300 mg on Day 15 if tolerated. On Day 22, they receive the first cycle of TSEB radiotherapy, given as 2 Gy over two consecutive days. Safety is assessed on Day 52, with efficacy evaluations on Days 52 and 82 using global response assessments including the modified Severity Weighted Assessment Tool (mSWAT). Patients with less than 70% reduction in mSWAT score may receive additional TSEB cycles of 4 Gy over two days, up to six cycles total. Treatment continues until disease progression, unacceptable side effects, physician recommendation, or study end. During the study, participants undergo safety and response evaluations including skin assessments with mSWAT scoring. The primary outcome measures the incidence of severe radiation dermatitis one month after treatment, while secondary outcomes assess overall skin response up to 82 days post-TSEB. The trial involves ongoing monitoring of treatment tolerance and disease status. Participants remain in the study until criteria for stopping treatment or study completion are met, with the expected study duration extending to March 2027.