Clinical Research Directory

New Double Epigenetic Regimen in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

This study is to investigate the therapeutic efficacy and side effect of chidamide, azacitidine combined with priming HAG regimen for relapsed or refractroy acute myeloid leukemia

Study Investigating the Safety of CD19 CAR-T Cells in Relapsed/Refractory AML Expressing CD19

Refractory/Relapsed (R/R) acute myeloid leukemia (AML) is associated with a dis-mal prognosis. In some subsets of AML such as AML driven by the t(8;21) translocation, leading to the RUNX1-RUNX1T1 (AML1-ETO) fusion transcript expression, CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 % of cases. Interestingly, the expression of the CD19 antigen is also detected in the CD34+ CD38-population leukemic stem cells. t(8;21) AML subtype has a rather good prognosis with an intensive chemotherapy regimen, but relapses occur in around 40 % of the patients and new therapeutic options are needed for these patients. Plesa et al, reported a successful treatment of a refractory t(8;21) AML with bispecific monoclonal antibodies that targets CD19. More recently, Danylesko et al, have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t(8;21) AML(1). The same group has just submitted an abstract of 6 treated patients to the European Haematology Association (EHA) 2023 meet-ing: Six patients (adults-5, child-1) with t(8; 21) AML (confirmed by cytogenetic and FISH) and aberrant CD19 expression were included. One patient had a complex karyotype. Molecular analysis for CKIT, NPM1, IDH1, IDH2, and CBPa were nega-tive in all pts. One pt harbors the FLT3 ITD and TKD mutations. Median number of previous chemotherapy (CT) lines was 4 (3-8). Four patients were with chemo re-sistant relapse post allo-HCT (MSD-1, 10/10 MUD -3) 5-18 months before CAR T-cell infusion. All patients developed CRS (grade 1-3) and were treated with i.v tocili-zumab and dexamethasone. 2/6 patients suffered from ICANS and were treated with steroids. In 4/6 patients, day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t(8;21) by FISH confirming clinical and cyto-genetic remission, while 2/6 pts with progressive AML had no response (Danylesko etal. Abstract EHA 2023, submitted). Interestingly, other subsets of AML display an aberrant expression of CD19. These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with R/R AML expressing this antigen. In this study, we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsed/refractory AML expressing CD19 for whom no curative alternatives are available. To this end, CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy (Miltenyi Biotec) in academic setting.

CLL-1 CAR-NK Cells for Relapsed/Refractory AML

This study is a single-arm, open-label, dose-escalation clinical trial aimed at exploring the safety, tolerability, and pharmacokinetic characteristics of the CLL-1 CAR NK cells, as well as providing preliminary observations on its efficacy in subjects with relapsed/refractory acute myeloid leukemia.

Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of R/R AML

The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of relapsed and/or refractory AML

Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia

The main purpose of this study is to identify a safe and potentially effective dose of tuspetinib to be used in future studies in study participants diagnosed with acute myeloid leukemia (AML), myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML) that is relapsed or refractory after at least one line of prior therapy, or in study participants with newly diagnosed AML. Tuspetinib will be administered as a single agent or in combination with other drugs (venetoclax or venetoclax plus azacitidine), as specified for each part of the study.

Specialty Compared to Oncology Delivered Palliative Care for Patients With Acute Myeloid Leukemia

This research study is evaluating whether primary palliative care is an alternative strategy to specialty palliative care for improving quality of life, symptoms, mood, coping, and end of life outcomes in patients with acute myeloid leukemia (AML).

Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia

Approximately 30% of adult AML subjects are refractory to induction therapy. Furthermore, of those who achieve CR, approximately 75% will relapse. FLT3-mutated AML comprise an especially poor prognosis group. Until now, there was no established standard for relapsed subjects with FLT3 mutations and less than 20% will achieve CR with subsequent treatment. In phase 3 Study ADMIRAL Trial, gilteritinib has resulted in CRc in over 25% of subjects receiving 120 mg/day before on study HSCT. With this treatment, the median overall survival is at 9.3 months, furthermore, gilteritinib was well tolerated at the proposed doses. This study has been designed for R/R patients for which gilteritinib as single agent has been showed to be superior to high- and low-intensity chemotherapy (Perl, NEJM 2019, Supp Table S4) and patients included in this study will receive this treatment. Beyond high- or low-intensity chemotherapy, other options available are best supportive car or other clinical trials. The aim of this study is to assess the efficacy and safety of the addition of oral-azacitidine to salvage treatment by gilteritinib in subjects ≥18 years of age with relapsed/refractory FLT3-mutated acute myeloid leukemia

Study of Oral PCLX-001 in R/R Acute Myeloid Leukemia

This is a dose-finding study of oral zelenirstat (PCLX-001) in patients with R/R AML. There are two parts to the study: Dose Escalation and Dose Expansion.