Clinical Research Directory

Long-Term Follow-Up of Subjects Treated With Seattle Children's Therapeutics Gene Therapy Products

Subjects exposed to gene therapy products (GTPs) may be at risk for delayed or long-term adverse events. This is a long-term follow-up (LTFU) protocol designed to evaluate the long-term safety of Seattle Children's Therapeutics (SCTx) GTPs and incorporates in monitoring guidance from the U.S. Food and Drug Administration (FDA). Subjects will be followed for up to 15 years starting from the date of the most recent infusion of an SCTx GTP. Subjects planning to receive, or who have received, at least one infusion of an SCTx GTP will be offered participation in this LTFU study. Subjects enrolled in this study will have safety assessments and laboratory evaluations performed at scheduled intervals for each unique SCTx GTP received. No treatment is administered in this LTFU study.

CD19/BAFF-R in Vivo CAR-T Cell Therapy Targeting Relapsed/Refractory B Cell Acute Leukemia/Malignant Lymphoma

The currently CAR-T cell therapy in clinical practice largely depends on the expansion of CAR-T cells in vivo. However, the in vitro preparation process of CAR-T cells is complex and costly. In vivo CAR-T cell therapy eliminates the need for ex vivo preparation, significantly reducing treatment costs and procedural complexity. It enables immediate use, thereby improving patient accessibility. CD19 is stably overexpressed in more than 90% of B-cell malignancies. BAFF plays a core regulatory role in the survival, maturation, and homeostasis maintenance of B cells. BAFF-R is selectively expressed on the surface of mature B cell subsets and most B-cell malignancies. Currently, BAFF-R-based CAR-T therapy is in preclinical and early clinical research stages, demonstrating promising therapeutic potential, particularly offering a novel treatment option for patients with CD19-negative or drug-resistant B-cell tumors. The use of CD19/BAFF-R in vivo CAR-T cells as a new anti-tumor therapy may provide a new research direction for the treatment of relapsed/refractory B-cell acute leukemia/malignant lymphoma.

Neurological and Cognitive Dysfunction Following CAR-T Treatment. ICANS and Beyond

This is a phase 4 non-interventional single center trial. We aim to prospectively include patients scheduled to undergo CAR-T therapy at ME CAST, Karolinska University Hospital Huddinge, to study ICANS. Because ICANS develops rapidly, inclusion during this potentially life-threatening phase would not be feasible; patients must therefore be enrolled before they start treatment. We aim to include patients who are clinically at high risk of developing ICANS. The risk of ICANS is assessed based on diagnosis, tumor burden, CAR-T product, and inflammatory status prior to treatment initiation. We plan to compare patients who develop ICANS grade 2-4 with patients who develop no ICANS or at most grade 1. Patients will undergo Positron Emission Tomography (PET) with two different tracers: (1) PBR28 for TSPO, which provides a measure of brain inflammation-this ligand binds to microglial cells-and (2) 11C-UCB-J for SV2A, which provides a measure of synaptic density in the brain. The results will be compared with magnetic resonance imaging. We will collect blood, bone marrow and cerebrospinal fluid (CSF) samples from this patient cohort. Samples will be taken from all patients before, during, and after CAR-T treatment. Participation in the study also includes computer-based cognitive testing, neuropsychological evaluation and genetic testing to determine whether the patient has receptors allowing binding of the TSPO radioligand used during PET imaging.

DALY II Japan/MB-CART2019.1 for DLBCL

DALY II Japan is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy.

Patient-Reported Outcomes in Allogeneic Stem Cell Transplantation and CAR-T Therapy

3.1. Overview Prospective, multicenter, observational cohort study comparing short-term PROs measured with the HM-PRO between two exposure groups: patients undergoing allogeneic stem cell transplantation (allo-SCT) and patients receiving CAR-T cell therapy. Patients will be enrolled at hospital admission for the index inpatient procedure and followed through the inpatient stay (admission → discharge). The study is non-randomized and designed to describe trajectories of symptoms and HRQoL and to estimate the between-group difference in deterioration of HM-PRO scores (primary estimand: mean difference in change score, CAR-T vs allo-SCT).

MB-CART2019.1 in Refractory Multiple Sclerosis

The goal of this trial is to assess the feasibility, safety and preliminary efficacy of MB-CART2019.1 in patients with active refractory primary and secondary progressive MS.

Study of BCMA/CD70 CAR-T Therapy for Refractory cSLE

This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-BCMA/CD70 CAR-T cells in the treatment of refractory systemic lupus erythematosus.