Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Evaluating APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With T-PLL

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: NCT04496349
Recruitment Status : Not yet recruiting
First Posted : August 3, 2020
Last Update Posted : May 6, 2021
Sponsor:
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

Brief Summary:
This is a multi-center, open-label, phase IIa study to evaluate the pharmacokinetics (PK), safety, and efficacy of APG-115 as a single agent or in combination with APG-2575 in patients with T-PLL. The study consists of two parts. A total of 24-36 T-PLL patients will be enrolled.

Condition or disease Intervention/treatment Phase
T-Prolymphocytic Leukemia Drug: APG-115 Drug: APG-2575 Phase 2

Detailed Description:

In Part 1, 12-18 participants will be enrolled using a 3+3 dose escalation design. Patients receive APG-115 orally once every day (QD) with meal on Days 1 to 5, and 23 days off in the 28-day cycles.

In Part 2, the recommended starting dose of APG-115 in combination with APG-2575 in Part 2 will be determined by pooling available dose, PK, pharmacodynamics (PD), safety, and efficacy data of Part I, and the consequent results of conducting an integrated dose-response and exposure-response analyses on the data from Part 1, after discussion between the sponsor and investigators. APG-2575 will be administered orally once every day (QD) with meal (low fat meal preferred) in a 28-day cycle following a daily ramp-up schedule.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study consists of Part 1 APG-115 as monotherapy and Part 2 APG-2575 in combination with APG-115 (APG-115 dose fixed). APG-115 and APG-2575 will be orally administrated on 28-day cycles. Totally 12-18 participants will be enrolled using a 3+3 dose escalation design. Patients receive APG-115 orally once every day (QD) with meal on Days 1 to 5, 23 days off on the 28-day cycles.The recommended dose of APG-115 used in combination with APG-2575 will be determined based on the data from Part 1 after discussion between the sponsor and investigators. APG-2575 will be administered orally once every day (QD) with meal (low fat meal preferred) in a 28-day cycle following a daily ramp-up schedule. Dose escalation uses a standard 3+3 design starting from 400 mg to 800 mg (400 mg, 600 mg, 800 mg). APG-115 will be given at a fixed dose and started after the daily ramp-up of APG-2575 is completed.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIa Study Evaluating the Pharmacokinetics, Safety and Efficacy of APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With Relapsed/Refractory T-cell Prolymphocytic Leukemia (R/R T-PLL)
Estimated Study Start Date : May 31, 2021
Estimated Primary Completion Date : May 31, 2023
Estimated Study Completion Date : May 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: APG-115 monotherapy
APG-115 will be given alone
Drug: APG-115
APG-115 given orally for first 5 consecutive days each cycle

Experimental: APG-115 + APG-2575 combination
APG-115 is given in combination with APG-2575
Drug: APG-115
APG-115 given orally for first 5 consecutive days each cycle

Drug: APG-2575
APG-2575 given orally each day in cycle




Primary Outcome Measures :
  1. Maximum tolerated dose of APG-115 [ Time Frame: 28 days ]
    To evaluate the safety of APG-115 as a single agent

  2. Maximum tolerated dose of APG-115+APG-2575 [ Time Frame: 28 days ]
    To evaluate the maximum tolerated dose of APG-115 and APG-2575 in combination



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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. Patients with relapsed/refractory T-PLL who have active disease and have received at least one prior therapy
  3. Patients must not have had chemotherapy or antibody therapy for 7 days prior to starting APG-115 and/or APG-2575. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
  4. Absolute neutrophil count (ANC) ≥ 500/mm˄3; hemoglobin ≥ 60 g/L; platelet count ≥ 30,000/mm˄3
  5. Total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless related to leukemic involvement
  6. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3× ULN or ≤ 5 × ULN unless related to leukemic involvement
  7. Adequate kidney function, defined as a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
  8. Require laboratory TLS parameters to be within acceptable range and clinical TLS parameters no higher than grade 2 at study baseline, with or without TLS treatment, before initiation of study treatment.
  9. Known cardiac ejection fraction of ≥ 45% within the past 3 months
  10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  11. Has no malignancies other than T-PLL that: 1) currently require systemic therapies; 2) were not previously treated with curative intention (unless the malignant disease is in a stable remission according to the discretion of the treating physician); 3) or developed signs of progression after curative treatment
  12. A negative serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling in this trial. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
  13. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his/her legally authorized representative is required prior to their enrollment on the protocol.

Exclusion Criteria:

  1. Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  2. Patient with documented hypersensitivity to any of the components of the therapy program.
  3. Patient previously treated with a murine double minute 2 (MDM2) inhibitor.
  4. Known active, uncontrolled central nervous system (CNS) malignancy
  5. Patients require graft versus host therapy, or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose of study drug).
  6. Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies)
  7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation. Hepatitis B virus deoxyribonucleic acid (DNA) and HCV ribonucleic acid (RNA) must be undetectable upon testing. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (i.e., hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
  8. Failure to have recovered (Grade > 1) (except alopecia and pigmentation) from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)
  9. Significant screening electrocardiogram (ECG) abnormalities including corrected QT interval (Fridericia) (QTcF) > 470 msec
  10. Patients who have any conditions or illness that, according to the opinions of the Investigators or the medical monitor, would compromise patient safety or interfere with the evaluation of safety and efficacy to the study drug(s).
  11. Patients who have used strong CYP2C8 inhibitors, or moderate or strong CYP3A4 inhibitors or inducers within washout period of 14 days or 7 half-lives before the first administration of study drugs, whichever is longer.

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): NCT04496349


Contacts
Layout table for location contacts
Contact: Kathryn Shantz 301-802-3414 kate.shantz@ascentage.com

Sponsors and Collaborators
Ascentage Pharma Group Inc.
Investigators
Layout table for investigator information
Study Chair: Yifan Zhai, MD, PhD Ascentage Pharma Group Inc.
Layout table for additonal information
Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT04496349    
Other Study ID Numbers: APG115TU101
First Posted: August 3, 2020    Key Record Dates
Last Update Posted: May 6, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Prolymphocytic
Leukemia, Prolymphocytic, T-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, T-Cell