Study of Prilinostat Mesylate for Injection in the Treatment of Relapsed or Refractory B Cell-related Tumor-predominant
Condition: Diffuse Large B Cell Lymphoma，DLBCL
MeSH terms: Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 1

Summary: 
      Purinostat mesylate for injection (PM) was the novel and highly potent Class I a and IIb
      HDAC-selective inhibitors. The results of regular blood sampling analysis of the mouse B-cell
      lymphoma model induced by ighmyc transgenic mice showed that the treatment of PM in each
      group reduced the proportion of peripheral blood tumor cells in mice. Therefore, PM has the
      potential to treat diffuse large B cell lymphoma.

      The results of in vitro enzymatic activity screening showed that PM has high inhibitory
      activity on HDAC tumors (including HDAC1, 2, 3, 8 subtypes) and type II HDACs (including
      HDAC6, 10 isoforms), which are closely related to tumors in the HDAC family. Therefore, the
      results of in vitro enzyme activity screening showed that the IC50 values of PM for
      inhibiting HDAC1, HDAC2, HDAC3, HDAC8, HDAC6, and HDAC10 subtypes of HDAC class I and HDAC
      class IIb were 0.81, 1.4, 1.7, 3.8, 11.5, and 11 nM, respectively. However, the inhibitory
      activity of HDAC IIa and HDAC IV enzymes was low, and its IC50 values for HDAC4, HDAC5,
      HDAC7, HDAC9, and HDAC11 subtypes of HDAC IIa and HDAC IV were 1072, 426, 590, 622, and 3349
      nM, respectively. These data means PM exist high selectivity for tumor-associated HDAC class
      I and HDAC IIb.

      Compared with the blank control group, the body weight of the tumor-bearing animals in each
      dose of PM group did not decrease seriously during the treatment process, and the animals
      were in good condition during the whole experiment, indicating that the PM is efficacy and
      safe.

      During the course of the experiment, the tumor cell population (GFP+, B220+) in the blood of
      the animals basically regressed after treatment with Prilistat hydrochloride.

      Research purposes:

      Main purpose:

      Observation of patients with relapsed or refractory hematological tumors (including but not
      limited to after standard therapy) mainly in patients with relapsed or refractory B
      cell-related tumors. Tolerability and safety of B-cell lymphoma, multiple myeloma, B-cell
      acute leukemia, T-cell lymphoma, T-cell acute leukemia) with disease progression or
      ineligible for standard therapy.

      To observe the dose-limiting toxicity (DLT) in patients with relapsed or refractory B
      cell-related tumors and hematological tumors, and determine its maximum tolerated dose (MTD),
      which is the maximum tolerated dose (MTD). Phase II clinical dosing schedule provides the
      basis.

      Secondary Purpose:

      To evaluate the pharmacokinetic parameters of patients with relapsed or refractory
      B-cell-related tumors and hematological tumors after single and multiple intravenous
      infusions of priinostat mesylate for injection.

      To evaluate the pharmacodynamics of patients with relapsed or refractory B cell-related
      tumors and hematological tumors after single and multiple intravenous infusions of priinostat
      mesylate for injection.

      To preliminarily observe the efficacy of Priinostat mesylate for injection in the treatment
      of patients with relapsed or refractory hematological tumors, mainly patients with B
      cell-related tumors.
    


Intervention name(s): Prilinostat Mesylate 1.2mg/m2; Prilinostat Mesylate 2.4mg/m2; Prilinostat Mesylate 4.0mg/m2; Prilinostat Mesylate 6.0mg/m2; Prilinostat Mesylate 8.4mg/m2; Prilinostat Mesylate 11.2mg/m2; Prilinostat Mesylate 15mg/m2
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.; 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.; 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.; 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.; 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.; 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.; 1 case,The starting dose,Take the medicine once on D1, D8, D11, D15.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other