Acute Myeloid Leukemia (AML)

OUTLINE: This is a dose-escalation study of 211\^At-BC8-B10. Patients receive 211\^At-BC8-B10 intravenously (IV) over 6-8 hours on day -7 and may receive 131\^I-BC8-B10 IV on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and peripheral blood stem cell (PBSC) transplant on day 0. Patients also receive cyclosporine orally (PO) or IV every 12 hours on days -3 to 56 and then tapered to day 180 (for patients with related donors), or continuing to day 96 and then tapered to day 150 (for patients with unrelated donors). Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6 hours after PBSC infusion) every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on day 0 and then reduced to every 12 hours on days 30-150 then tapered to day 180 (for patients with unrelated donors). Patients may undergo single photon emission computed tomography (SPECT), bone marrow aspirate sample and blood sample collection on study. After completion of study treatment, patients are followed up at 100 days and then at 6, 9, 12, 18 and 24 months.

OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody BC8-B10. PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine intravenously (IV) over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Patients also undergo TBI on day -1. TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or PO three times daily (TID) on days 5-35, and tacrolimus IV over 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per physician discretion. Patients also begin granulocyte colony-stimulating factor (G-CSF) IV or subcutaneously (SC) on day 5 to continue until absolute neutrophil count (ANC) \> 1000/mm\^3 x 3 days. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. After completion of study treatment, patients are followed up at day 100, and at 6, 9, 12, 18, and 24 months.

PRIMARY OBJECTIVES: I. Describe toxicities attributable to actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-anti-CD38 daratumumab) radioimmunotherapy by dose level in patients treated under this regimen. II. Determine the maximum tolerated dose/recommended phase II dose (MTD/RP2D) of 225Ac-DOTA-anti-CD38 daratumumab radioimmunotherapy with fixed doses of organ sparing TMLI (12 Gy), fludarabine and melphalan (FM100) as conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) for treatment of high-risk acute myeloid leukemias, acute lymphoblastic leukemia or myelodysplastic syndrome (MDS), in patients who are not eligible for standard myeloablative regimens. SECONDARY OBJECTIVES: I. Evaluate the safety of the regimen, at each dose level, by assessing the following: Ia. Type, frequency, severity, attribution, time course and duration of adverse events, including acute/chronic graft-versus-host disease (GVHD), infection and delayed engraftment. II. Estimate overall survival (OS), event-free survival (EFS), GVHD relapse free survival (GRFS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years. III. Describe biodistribution, pharmacokinetics and organ dosimetry of 225Ac-DOTA-daratumumab. OUTLINE: This is a dose escalation of actinium Ac 225-DOTA-Daratumumab in combination with fludarabine, melphalan and TMLI. Patients receive daratumumab intravenously (IV) over 45 minutes followed by indium In 111-DOTA-daratumumab IV over 15 minutes and actinium Ac 225-DOTA-daratumumab IV over \~20-40 minutes on day -15. Patients receive TMLI twice daily (BID) on days -8 to -5, fludarabine IV on days -4 to -2 and melphalan IV on day -2, followed by HCT on day 0. Patients receive GVHD prophylaxis with sirolimus and tacrolimus starting on day -1. Patients also undergo computed tomography (CT) during screening, nuclear scan and single photon emission computed tomography (SPECT) scans on study, bone marrow biopsy and aspiration, echocardiography, or multigated acquisition scan (MUGA), and blood sample collection during screening and throughout study. After completion of study treatment, patients are followed up twice weekly for the first 100 days post-transplant, then twice monthly up to 6 months post-transplant followed by monthly until discontinuation of immunosuppressive therapy without evidence of GVHD with at least yearly follow-up for 2 years.

OBJECTIVES: Primary * Evaluate the use of 3'-deoxy-3'-\[18F\] fluorothymidine (FLT) positron emission tomography (PET) imaging to measure tumor proliferation and the DNA synthetic pathway (thymidine kinase levels) in patients with cancer. Secondary * Determine the efficacy of FLT PET imaging in detecting lesions and estimating response to treatment. OUTLINE: Patients undergo up to four 3'-deoxy-3'-\[18F\] fluorothymidine positron emission tomography imaging procedures.

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of a regimen combining 8-chloro-adenosine (8-Cl-Ado) and venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML), including type, frequency, severity, attribution, and duration of the toxicity. II. Establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of 8-Cl-Ado when given in combination with venetoclax. SECONDARY OBJECTIVES: I. Obtain preliminary estimates of the anti-leukemia activity of the 8-Cl-Ado/venetoclax regimen by assessing the overall response rate (Complete remission\[CR\]+ complete remission with incomplete hematologic recovery \[CRi\]+ partial response \[PR\]) and complete remission rate (CR+CRi). II. Obtain preliminary estimates of duration of remission (DOR), overall survival (OS), and event-free survival (EFS). III. Determine the pharmacokinetics (PK) of plasma 8-Cl-Ado and metabolites when 8-Cl-Ado is given in combination with venetoclax. EXPLORATORY OBJECTIVES: I. Evaluate PK and pharmacodynamics (PD) of VEN/8-Cl-Ado combination therapy to identify biomarkers of clinical response and resistance. II. Identify genes and pathways associated with response to VEN/8-Cl-Ado. III. Determine the metabolic consequences of VEN/8 Cl-Ado treatment on leukemia stem cells (LSCs). OUTLINE: Patients receive 8-Cl-Ado intravenously (IV) over 4 hours daily on days 1-5 and venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 28 days for up to 1 year.

This is a multicenter, open-label, phase I study aimed to evaluate the safety, tolerability, pharmacokinetics（PK）, Pharmacodynamics（PD）, preliminary anti-tumor activity and immunogenicity of SCTC21C in patients with relapsed or refractory CD38+ hematologic malignancies.The study includes Dose-finding stage and Dose-expansion stage. In Dose-finding stage, participants will be assigned to receive sequentially higher doses of SCTC21C ranging from 0.01 to 960mg. In Dose-expansion stage, total of at least 20 participants will be randomly assigned to receive two different doses of SCTC21C at a ratio of 1:1.All participants will receive the treatment until disease progression or unacceptable drug-related adverse events.

This is a single-arm, open-label, phase I dose-escalation clinical study to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual-target CAR T cell injection in r/r AML subjects. The main purpose of this study is to evaluate the safety of CLL1 and CD38 dual - target CAR - T cell injection in the treatment of r/r AML and the study contains two phases with the first phase adopting an ATD design and the second phase adopting a 3+3 design.

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety and efficacy of CD33 CAR-T Cell in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 15-27 participants in this trial.

This study evaluates the safety and tolerability of escalating doses of BP1002 (Liposomal Bcl-2 Antisense Oligodeoxynucleotide) in patients with refractory/relapsed AML. The study is designed to assess the safety profile, identify DLTs, biologically effective doses, PK, PD and potential anti-leukemic effects of BP1002 as single agent (dose escalation phase) followed by assessing BP1002 in combination with decitabine (dose expansion phase).

This study is a clinical trial to evaluate the tolerability and pharmacokinetics of TQB3455 tablets in patients with hematological malignancies. TQB3455 is an isocitrate dehydrogenase 2(IDH2) inhibitor . This project is divided into two stages. The first stage aims to evaluate the safety and tolerability of single or multiple oral administration of TQB3455 tablets in subjects with malignant hematological tumors. The second phase aims to evaluate the efficacy and safety of TQB3455 tablets alone or in combination with azacitidine in subjects with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).