Clinical Research Directory

Leukapheresis for CAR or Adoptive Cell Therapy Manufacturing

Background: Leukapheresis is a procedure to separate and collect white blood cells. It is the first step in a treatment called CAR (chimeric antigen receptor) T-cell therapy. CAR-T therapy may be offered to people when their cancer comes back. The collected T-cells are used to make a special version of T-cells called CARs. Researchers want to collect these cells from people who may become eligible for a CAR T-cell study in the future. Objective: To identify people who have a high likelihood to benefit from CAR T-cell therapy early in their disease course and collect and store a T-cell product. Eligibility: People ages 3-65 with a form of leukemia or lymphoma that has not been cured by standard therapy Design: Participants will be screened with medical history, physical exam, and blood and urine tests. Review of existing MRI, x-ray, pathology specimens/reports or CT images may be done. On this study, participants will have leukapheresis. A needle will be placed into the arm. Blood will be collected and go through a machine. White blood cells will be taken out by the machine. The plasma and red cells will be returned to the participant through a second needle in the other arm. The procedure will take 4-6 hours. Some participants may have a central line (catheter) inserted which is needed to do the leukapheresis procedure, instead of the needles in the arms-especially if they are smaller. For a central line placement, a long thin tube is inserted through a small incision into the main blood vessel leading into the heart that would allow access to the blood to do the leukapheresis procedure. Participants cells will be processed and frozen for future use in a CAR T-cell therapy study. ...

CNS-Relapse Prevention in High-Risk Diffuse Large B-cell Lymphoma With Thiotepa-based Autologous Stem Cell Transplant

A serious consequence of systemic diffuse large B-cell lymphoma (DLBCL) is secondary central nervous system (CNS) relapse, which occurs in approximately 5% of all patients. Many CNS relapses occur within the first year after completion of frontline treatment and are associated with significantly increased mortality; thus, it is important to tailor frontline treatment to provide prophylaxis against CNS relapse in those patients who are determined to be high-risk. Autologous stem cell transplantation (ASCT) is standard of care for patients with DLBCL who relapse one year or more after first remission, and it has been shown to improve progression-free survival for patients with primary CNS lymphoma. The four-drug BEAM regimen (carmustine, etoposide, cytarabine, and melphalan) is the preferred conditioning regimen for DLBCL patients undergoing ASCT; however, patients with primary CNS lymphoma receive thiotepa plus carmustine as their conditioning regimen due to its better CNS penetration. This study tests the hypothesis that consolidation thiotepa/carmustine ASCT in first complete remission will reduce the risk of CNS relapse in transplant-eligible patients with DLBCL with no prior CNS disease at high risk of secondary CNS recurrence.

19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers

The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of 19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find this dose, they can test it in future participants to see if it is effective in treating their relapsed/refractory B-cell cell cancers. This study will also look at whether 19(T2)28z1xx CAR T cells work against participants' cancer.

Pilot Study of Anti-CD19 Chimeric Antigen Receptor T Cells (CAR-T Cells) for the Treatment of Relapsed/Refractory CD19+ Malignancies

This is an open label, non-randomized, phase 1 study of anti-CD19 CAR-T cells against relapsed CD19 positive NHL, CLL and ALL based in a lymphodepletion regimen (fludarabine and cyclophosphamide) and using a CellReGen-based process for manufacturing CAR-T cells. This study will utilize a staggered enrollment design with a safety observation period.

A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies

Study consists of two main parts to explore tacabrutideg recommended dosing, a Phase 1 monotherapy dose finding comprised of monotherapy dose escalation and monotherapy safety expansion of selected doses, and a Phase 2 (expansion cohorts)

A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of DZR123 (Tulmimetostat, CPI-0209), both as monotherapy and in combination with enzalutamide, in patients with advanced solid tumors and lymphomas.

Split-Dose R-CHOP for Older Adults With DLBCL

This study is investigating a new administration schedule of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) chemotherapy for participants with Diffuse Large B-Cell Lymphoma (DLBCL), focusing on an underserved elderly population (aged 75 and up; certain participants 70-74 may be eligible) that is often excluded from clinical trials. Participants can expect to be on study for 2.5 years (treatment for 6 months and 2 years of post treatment follow-up).

Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor for Lymphoma

This is a Phase I, open-label multi-site trial designed to evaluate the safety of administering rapidly-generated Tumor associated antigen specific T cells (TAA-T) with the Programmed Death1 (PD-1) inhibitor Nivolumab, in relapsed/refractory lymphoma (rel/ref) patients with measurable disease (group A) or as adjunctive therapy following autologous hematopoeitic stem cell transplant(HSCT) for patients at high risk of relapse (group B). The purpose of this study is to find out if the tumor specific T cells given with Nivolumab are safe and to learn what the side effects are and if the combination can help patients with relapsed lymphomas.

Feasibility and Safety of Collecting and Combining Autologous Hematopoietic Stem Cells With Chimeric Antigen Receptor (CAR) T-Cell Therapy in Subjects With Relapsed/Refractory Hematological Malignancies

The study is designed to examine the feasibility and safety of collecting autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy for patients with relapsed/refractory (r/r) hematological disease. The study will evaluate feasibility of collecting the target dose of HSCs from at least 50% of enrolled patients. The study will assess safety based on incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the first 60 days post CAR T dosing, and also through the collection of adverse events (AEs) and serious adverse events (SAEs) as well as the durability of response after treatment with HSCs with CAR T. The study follows an open-label, single-center and single non-randomized cohort design. 20 subjects with r/r hematological malignancies will be enrolled and treated to evaluate the feasibility and preliminary safety of collecting autologous HSCs and combining them with CAR T-cell therapy.

Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)

This is a Phase 1/2, first-in-human, open-label, dose-escalating trial designed to assess the safety and efficacy of VNX-101 in patients with relapsed or refractory CD19-positive hematologic malignancies.

LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

This is a phase I, interventional, single arm, open label, treatment study designed to evaluate the safety and efficacy of LV20.19 CAR -T cells with pirtobrutinib bridging and maintenance in adult patients with B cell malignancies that have failed prior therapies.

Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)

The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) in Japanese participants with relapsed, progressive or refractory B-cell lymphomas and Japanese participants with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior standard of care (SOC). The trial consists of two parts: Part 1, dose escalation (phase 1), and Part 2, expansion (phase 2). The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase-2 dose (RP2D), as well as to establish the safety profile of epcoritamab in Japanese participants with relapsed, progressive or refractory B-cell lymphoma and Japanese participants with B-cell lymphomas that have achieved PR or CR. In the expansion part, additional participants will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab. Part 2 of the trial will be initiated once the RP2D has been determined in Part 1. In Part 2, epcoritamab is investigated as a monotherapy and in combination with other SOC agents.

DZD8586 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (TAI-SHAN9)

This study will treat patients with DLBCL whose disease comes back or is not responding to prior therapy. This study will assess the anti-tumor activity of DZD8586 as monotherapy. It will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body.

Pivotal Study to Validate a Novel System to Non-Invasively Detect Severe Neutropenia

Pivotal study to validate the diagnostic performance of PointCheck, the first non invasive device to preliminary detect neutropenia in cancer patients receiving intermediate/high risk antineoplastic therapy.

Copanlisib in Combination With Rituximab and CHOP Chemotherapy in Patients With Previously Untreated DLBCL

This is a prospective, multicenter, non-randomized, open-label, phase II study to describe the efficacy of R-CHOP plus copanlisib including a safety run-in phase in order to detect early and common unexpected toxicities caused by the addition of copanlisib to the standard immuno-chemotherapy R-CHOP in patients with diffuse large B-cell lymphoma (DLBCL)

IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas

This first-in-human study will evaluate the recommended dose for further clinical development, safety, tolerability, antineoplastic activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS03, a CD19 targeting antibody-drug conjugate, in patients with advanced B cell non-Hodgkin lymphoma (NHL).

Role of the Gut Microbiome in the Outcome of Diffuse Large B-Cell Lymphoma Patients Treated With CAR-T Cell Therapy

Despite impressive outcomes in selected patients, significant heterogeneity in clinical response to CAR-T cell therapy remains. The gut microbiome (GM) has recently emerged as one of the key modifiable factors of prognosis and response to treatment in cancer patients, with high-diversity profiles rich in health-associated taxa while poor in pathobionts generally associated with better response and longer survival. Currently, it is unknown if GM also modulates anti-tumor responses to CAR-T cells and related toxicities in lymphomas.

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies

This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.

Rituximab (Rtx) + Tafasitamab in Combination With Allogeneic NK Cells for Treatment of Relapsed/Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)

This research study is for people who have relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) that has not responded to two or more lines of therapy. The purpose of this study is to identify the recommended dose of allogeneic NK cells in combination with IL-2, Tafasitamab and Rituximab for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma. NK cells are an investigational (experimental) treatment which means they are not approved by the Food and Drug Administration (FDA). NK cells are a type of lymphocyte that's part of the body's natural immune system, and they can kill cancer cells by creating pores in the cancer cell membranes and inducing apoptosis (programmed cell death). Participants in this study will receive lymphodepleting chemotherapy, as well as Allogeneic NK cells, Tafasitamab and Interleukin-2 (IL-2) by an intravenous (IV) infusion. Participants are expected to complete one cycle, and they may be eligible to complete a second cycle of the same regiment if they have stable disease, partial or complete remission at the end of the first cycle. Participants will be in this study for about 12 months.

Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

This phase II study will evaluate whether a reduction in radiation dose and field size will maintain a high rate of local control while minimizing the risk of acute and late toxicity . Hypothesis: The radiation dose and treatment volume can be safely reduced from 30 Gy to 20 Gy while maintaining high rates of local control in patients who had a negative PET-CT scan following rituximab - containing chemotherapy.

Thrombosis in Diffuse Large B-cell Lymphoma:the PREDIC-TO (PREDICt ThrOmbosis) Study

Comparative Evaluation of Thrombotic Risk Models in DLBCL patients Objective: To assess the impact of thrombotic risk factors and compare the performance of existing predictive models (Khorana, Throly, Model IX) in Diffuse Large B-cell Lymphoma (DLBCL) Primary Endpoints: Measure thrombotic risk factors in existing models Determine occurrence, type, and timing of venous thrombotic events Secondary Endpoints: Assess performance of models in patients without thrombotic events at diagnosis Evaluate dynamic risk factors during DLBCL treatment Identify additional risk factors not included in published models Analyze overall survival and VTE-free survival Methodology: Real-world cohort study of DLBCL patients Collection of static and dynamic risk factors Correlation analysis of risk factors with thrombotic events Development and validation of DLBCL-specific predictive model Conclusion: This study aims to compare existing predictive models and develop a DLBCL-specific model to aid in identifying high-risk patients and inform thromboprophylaxis decisions. Results will contribute to improved understanding and management of thrombotic risk in DLBCL.

Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma

The goal of this clinical trial is to study the addition of Acalabrutinib to standard R-miniCHOP in older adults with DLBCL. The main question it aims to answer is whether progression free survival kann be prolonged with the addition of Acalabrutinib. Participants will be randomised to receive either R-miniCHOP alone or R-miniCHOP with Acalabrutinib.

Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).

Is Trogocytosis a Predictive Marker of CAR-T Cell Response in Diffuse Large B-cell Lymphoma?

CAR-T cell therapy has improved survival in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL R/R). However, only 65% of patients achieve a complete metabolic response after this treatment. To date, there is no predictive test for therapeutic response after injection of CAR-T cells. Recent studies have shown that the level of trogocytosis by immune cells correlates with the persistence of tumor cells in patients with hematological malignancies. Our main objective is to identify a phenotypic "signature" of trogocytosis predictive of therapeutic response 6 months after injection of CAR-T cells for DLBCL.