Clinical Trials /

APG-2575 Study of Safety, Tolerability ,PK/PD in Patients With Hematologic Malignancies

NCT03537482

Description:

This is a multi-center, single-agent, open-label, Phase I study of APG-2575. The study consists of the dose escalation stage and the dose expansion stage.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: APG-2575 Study of Safety, Tolerability ,PK/PD in Patients With Hematologic Malignancies
  • Official Title: A Phase I Study of Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Property of Orally Administered APG-2575 in Patients With Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: APG-2575
  • NCT ID: NCT03537482

Conditions

  • Hematologic Malignancies

Interventions

DrugSynonymsArms
APG-2575single-agent, open-label, Phase I study of APG-2575

Purpose

This is a multi-center, single-agent, open-label, Phase I study of APG-2575. The study consists of the dose escalation stage and the dose expansion stage.

Detailed Description

      APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycles.
      Initially, the start dose is 20mg. Single patient cohorts will be evaluated, the dose of
      APG-2575 will be increased in subsequent cohorts, to 50 mg, 100 mg, 200 mg, 400 mg, 600mg and
      800mg accordingly. If there is any one of the following event is observed, a DLT, two drug
      related Grade 2 toxicities or one drug related ≥ Grade 3 toxicity, or laboratory or clinical
      TLS, or suspected hypersensitivity reaction occur in Cycle 1, or dose level of 400 mg is
      reached, the dose escalation will convert to the standard 3+3 design, If ≥ 2/6 patients
      develop DLT at any dose level dose escalation will cease and the dose level immediately below
      will be expanded to 6 patients. If ≤ 1/6 patients develop a DLT at the highest dose reached
      this will be declared the MTD. After the MTD is defined, a maximum of 20 patients will be
      treated at that dose level.
    

Trial Arms

NameTypeDescriptionInterventions
single-agent, open-label, Phase I study of APG-2575ExperimentalThe study consists of the dose escalation stage and the dose expansion stage
  • APG-2575

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years old.

          2. Histologically confirmed diagnosis of either one of the B-cell hematologic
             malignancies including multiple myeloma, chronic lymphocytic leukemia,
             lymphoplasmacytic lymphoma, and non-Hodgkin's lymphoma such as mantle cell lymphoma,
             diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM) and acute myeloid
             leukemia

          3. Patient must have relapsed or refractory to, intolerant to, or are considered
             ineligible for therapies known to provide clinical benefit. In addition,

             a. AML Patients will be eligible if they have failed standard induction regimen, are
             not considered candidate for further chemotherapy or stem cell transplantation or have
             primary refractory AML.

          4. Life expectancy ≥ 3 months.

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose
             escalation ; 0-2 in dose expansion.

          6. QTc interval ≤450ms in males, and ≤470ms in females.

          7. Adequate bone marrow function independent of growth factor:

          8. Absolute neutrophil count (ANC) ≥1.0 X 109/L.

          9. Hemoglobin ≥ 8.0 g/dL.

         10. Platelets count ≥ 30 X 109/L (entry platelet count must be independent of transfusion
             within 7 days of first dose).

         11. Adequate renal and liver function as indicated by:

        Exclusion Criteria:

        Patients who meet any of the following exclusion criteria are not to be enrolled in this
        study:

          1. Prior history of allogeneic cell transplant.

          2. Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or
             lymphoblastic lymphoma/leukemia.

          3. Received chemotherapy within 14 days (42 days for nitrosoureas or mitomycin C) prior
             to entering the study.

          4. Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or
             other anti-cancer therapy within 21 days of study entry.

          5. Radiation within 14 days of study entry, thoracic radiation within 28 days of study
             entry.

          6. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the
             opinion of the Investigator.

          7. Has known active central nervous system (CNS) involvement.

          8. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not
             recover to ≤ Grade 1 except alopecia or neuropathy.

          9. Concurrent treatment with an investigational agent, 14 days for small molecular agents
             and/or 28 days for biologics treatment prior to the first dose of therapy.

         10. Failure to recover adequately, as judged by the investigator, from prior surgical
             procedures. Patients with active wound healing, patients who have had major surgery
             within 28 days from study entry, and patients who have had minor surgery within 14
             days of study entry.

         11. Unstable angina, myocardial infarction, or a coronary revascularization procedure
             within 180 days of study entry.

         12. Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic
             infections, or any other disease or condition associated with chronic inflammation.

         13. Active infection requiring systemic antibiotic/ antifungal medication, known
             clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV
             disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:28 days
Safety Issue:
Description:Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0

Secondary Outcome Measures

Measure:Maximum plasma concentration (Cmax)
Time Frame:28 days
Safety Issue:
Description:Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:28 days
Safety Issue:
Description:Area under the plasma concentration versus time curve (AUC) of APG-2575 will be assessed in the patients treated with APG-2575
Measure:Anti-tumor effects of APG-2575
Time Frame:up to 2 years
Safety Issue:
Description:Response will be evaluated every 2 cycles (8 weeks), by the investigator based on disease specific criteria.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ascentage Pharma Group Inc.

Last Updated

February 15, 2019