Clinical Research Directory

Collection of Human Samples to Study Hairy Cell and Other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment

Background: \- Researchers who are studying hairy cell leukemia, and how the disease compares with other disorders, are interested in obtaining additional samples from leukemia patients and healthy volunteers. The investigators are particularly interested in samples from individuals who have diseases that can be treated with a new type of drug called immunotoxin, in which an antibody carrying a toxin binds to a cancer cell and allows the toxin to kill the cell. Objectives: \- To collect a variety of clinical samples, including blood, urine, lymph samples, and other tissues, in order to study the samples and develop new treatments for leukemia. Eligibility: \- Individuals 18 years of age and older who have been diagnosed with leukemia or other kinds of blood and lymphatic system cancers, or who are healthy volunteers. Design: * Individuals who have leukemia will be asked to provide blood, bone marrow, urine, and tumor tissue samples as requested by the researchers. Healthy volunteers will provide only blood and urine samples. * No treatment will be given as part of this protocol.

JAK1 Inhibitor Golidocitnib for the Treatment of Relapsed/Refractory Indolent T/NK-cell Lymphomas

Indolent T/NK-cell lymphomas are a heterogeneous group of lymphoproliferative diseases originating from T/NK cells, characterized by slow growth and proliferation, but currently remain incurable. For indolent T/NK-cell lymphomas that are unresponsive to first-line treatment, there are few treatment options available and the prognosis is poor. This study is an open-label, prospective clinical trial aimed at evaluating the feasibility, efficacy, and safety of PI3K inhibitors in the treatment of relapsed/refractory indolent T/NK-cell lymphomas. Patients will be treated with Golidocitnib, with an expected overall response rate of 60% for JAK1 inhibitor Golidocitnib treatment.

A Phase 1, Multicenter, Open-label, Prospective, First-in-human Dose-escalation Clinical Trial of Domain Therapeutics' Anti-CCR8 Monoclonal Antibody (DT-7012) in Patients With Relapsed or Refractory Cutaneous T-cell Lymphomas (CTCL)

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphomas characterized by a primary involvement of the skin. Among them, mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes. SS is defined as erythroderma (erythema of the entire skin surface), and circulating tumor blood cells. The circulating tumor T cells express CD4 and may lose expression of CD7 and CD26, while exhibiting in most cases aberrant expression of CD158k (KIR3DL2), which is a surface marker of Sézary cells. CCR8 is a surface marker of tumor-infiltrating regulatory T cells. It has recently be observed that CCR8 was expressed by tumor cells in CTCL and other peripheral T-cell lymphomas. CCR8 is expressed by skin resident-memory T cells which are believed to be the tumor cell-of-origin in mycosis fungoides. Domain Therapeutics (DT) showed the in vitro efficacy of their proprietary anti-CCR8 mAb DT7012 in the depletion of CTCL cells. Therapeutic depletion of CCR8-expressing cells by DT-7012 could eliminate tumor cells and activate the anti-tumor immunity in CTCL. We hypothesize that treatment with DT-7012 is effective in the treatment of relapsed or refractory (R/R) CTCL as advanced MF and SS.

Brentuximab Vedotin in CutAneous T-cell Lymphomas (CTCL): Post-allogeneic Hematopoietic Stem Cell Transplant Maintenance

Allogeneic hematopoietic stem cell transplantation (alloHSCT) showed efficacy in advanced-stage, high-risk, treatment sensitive cutaneous T-cell lymphomas (CTCL) in a prospective, propensity score-matched controlled study (CUTALLO) published by our group in the Lancet in 2023. Nevertheless, it is associated with a high rate of early relapse, with 2-year progression-free survival around 30%. Brentuximab vedotin (BV) has shown efficacy in the treatment of CD30-expressing CTCL after at least one prior systemic treatment in the ALCANZA trial and is market approved in this indication in Europe and the United States of America. BV has been successfully used as salvage treatment in the post-transplant setting in advanced CTCL. It has been shown that 90% of CTCL express CD30. To reduce the incidence of post-allograft relapse, we propose to assess the routine use of BV post-allograft in adult patients with advanced CD30-expressing mycosis fungoides-CTCL, who have received at least one line of prior systemic therapy, compared to placebo. Switch will be allowed from placebo to BV in case of disease progression. This project is supported by well-organized research networks with a strong track-record of published results in the field: French Study Group on Cutaneous Lymphomas (GFELC, Groupe Français d'Etude des Lymphomes Cutanés), INCa-labelled national rare cancers network; and the French Society of Bone Marrow Transplantation and CellTherapy. In the post-transplant setting, the current state-of-the-art practice is to treat patients once they have relapsed post-allogeneic transplant, whereas no prophylactic treatment is given at the time in the absence of characterized disease relapse. This ethically and scientifically justifies the proposal to evaluate whether earlier, prophylactic treatment with BV increases progression-free survival compared to placebo.