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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03537482
Recruitment Status : Recruiting
First Posted : May 25, 2018
Last Update Posted : March 30, 2020
Sponsor:
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

Tracking Information
First Submitted Date  ICMJE March 27, 2018
First Posted Date  ICMJE May 25, 2018
Last Update Posted Date March 30, 2020
Actual Study Start Date  ICMJE August 7, 2018
Estimated Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]
Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
  • Maximum plasma concentration (Cmax) [ Time Frame: 28 days ]
    Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: 28 days ]
    Area under the plasma concentration versus time curve (AUC) of APG-2575 will be assessed in the patients treated with APG-2575
  • Anti-tumor effects of APG-2575 [ Time Frame: up to 2 years ]
    Response will be evaluated every 2 cycles (8 weeks), by the investigator based on disease specific criteria.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE APG-2575 Study of Safety, Tolerability ,PK/PD in Patients With Hematologic Malignancies
Official Title  ICMJE A Phase I Study of Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Property of Orally Administered APG-2575 in Patients With Hematologic Malignancies
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
dose escalation and dose expansion after MTD
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematologic Malignancies
Intervention  ICMJE Drug: APG-2575
APG-2575 will be administered as an oral tablet
Study Arms  ICMJE Experimental: single-agent, open-label, Phase I study of APG-2575
The study consists of the dose escalation stage and the dose expansion stage
Intervention: Drug: APG-2575
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 15, 2018)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2020
Estimated Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yifan Zhai, MD 2405056608 yzhai@ascentagepharma.com
Contact: Bo Huang, MD bhuang@ascentagepharma.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03537482
Other Study ID Numbers  ICMJE APG2575-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ascentage Pharma Group Inc.
Study Sponsor  ICMJE Ascentage Pharma Group Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ascentage Pharma Group Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP