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

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ClinicalTrials.gov Identifier: NCT03537482
Recruitment Status : Recruiting
First Posted : May 25, 2018
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

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.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Drug: APG-2575 Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Intervention Model Description: dose escalation and dose expansion after MTD
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Property of Orally Administered APG-2575 in Patients With Hematologic Malignancies
Actual Study Start Date : August 7, 2018
Estimated Primary Completion Date : June 15, 2019
Estimated Study Completion Date : June 15, 2020

Arm Intervention/treatment
Experimental: single-agent, open-label, Phase I study of APG-2575
The study consists of the dose escalation stage and the dose expansion stage
Drug: APG-2575
APG-2575 will be administered as an oral tablet




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: 28 days ]
    Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575

  2. 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

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03537482


Contacts
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Contact: Yifan Zhai, MD 2405056608 yzhai@ascentagepharma.com
Contact: Yingjie Huang, MD 6095787515 yjhuang@ascentagepharma.com

Locations
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United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Sikander Ailawadhi, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, Texas
MDACC Recruiting
Houston, Texas, United States, 77030
Australia
St. Vincent Hospital Recruiting
Melbourne, Australia
Sponsors and Collaborators
Ascentage Pharma Group Inc.

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Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT03537482     History of Changes
Other Study ID Numbers: APG-2575
First Posted: May 25, 2018    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms