Trial Title:
Phase IIa Study to Assess Safety and Efficacy in the Relapsed/Refractory Acute Myeloid Leukemia
NCT ID:
NCT06532058
Condition:
Relapsed/Refractory Acute Myeloid Leukemia (R/R-AML)
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Azacitidine
Venetoclax
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
a single-arm, open, multicenter Phase IIa study with dose escalation and dose extension
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
QHRD107 capsule，Venclexta and Azacitidine
Description:
QHRD107（orally），Venclexta（orally），Azacitidine（subcutaneous injection）
Arm group label:
Part-A (Cohort 1-3)
Arm group label:
Part-B (Cohort 1-2)
Other name:
CDK9 inhibitors
Summary:
The purpose of this study is to assess the safety and efficacy of QHRD107 capsule
combined with Venclexta and azacitidine in the treatment of relapsed/refractory acute
myeloid leukemia: a single-arm, open, multicenter Phase IIa study
Detailed description:
This study is a single-arm, open, multicenter phase IIa clinical study, which is divided
into two stages: the dose-increasing study phase and the dose-expanding exploration
phase. The purpose of the dose-escalation phase is to explore the safety and tolerability
of QHRD107 capsule（40mgBID,60mgBID and 80mgBID） combined with Venclexta and azacitidine,
to evaluate the efficacy of the three-drug combination in subjects with
relapsed/refractory acute myeloid leukemia (R/R-AML), and to explore the pharmacokinetic
characteristics of the combination. The dose expansion stage aims to further evaluate the
safety, efficacy, pharmacodynamics and pharmacokinetics of QHRD107 capsule（60mgBID and
80mgBID）combined with Venclexta and azacitidine on the basis of exploring the safe dose
range determined in the dose escalation stage, and determine the recommended dose for
subsequent clinical studies
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Understand and voluntarily sign informed consent;
2. Age 18 and above;
3. Subjects with confirmed International Consensus Classification (ICC)
relapsed/refractory acute myeloid leukemia (R/R-AML) :
Recurrence was defined as the recurrence of leukemia cells in peripheral blood or
≥5% of bone marrow original cells after complete response (except for other reasons
such as bone marrow regeneration after consolidation chemotherapy) or the occurrence
of extramedullary leukemia cell infiltration.
Refractory is defined as meeting any of the following criteria:
1. Initial treatment cases that failed after 2 courses of treatment with standard
protocols;
2. Relapse within 12 months after complete remission (CR) after consolidation and
intensive treatment;
3. Recurrence after 12 months but failed to respond to conventional chemotherapy;
4. Two or more relapses.
4. ECOG evaluation ≤2 points;
5. Expected survival ≥3 months;
6. White blood cell (WBC) count <25×109 cells /L (hydroxyurea is allowed to control the
white blood cell count before treatment);
7. Subjects must have adequate liver function: total bilirubin (TBIL) ≤1.5× upper limit
of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
≤2.5×ULN;
8. Subjects must have adequate renal function: creatinine clearance ≥50 mL/min
(calculated using the Cockroft-Gault formula);
9. The subject has recovered from previous therapeutic toxicity to < grade 2 (according
to CTCAE 5.0 criteria), excluding primary disease effects. The following are
excluded: hair loss, fatigue, hyperpigmentation, stable hypothyroidism with hormone
replacement therapy, peripheral nerve toxicity after chemotherapy;
10. Eluting period from the first administration of antitumor therapy: a) At least 2
weeks between the end of cytotoxic chemotherapy drug treatment; b) Non-cytotoxic
drugs should be separated by at least 5 half-lives (if the duration of 5 half-lives
exceeds 4 weeks, the washout period is still measured by 4 weeks), and the interval
> 4 weeks shall prevail if the half-life is not clear; c) Anti-tumor Chinese
medicine at least 2 weeks interval;
11. Ability to understand and conduct visits, treatments, laboratory tests, and other
research procedures as planned;
12. Male/female subjects with reproductive potential must use effective contraception
from the date of signing the informed consent until 6 months after the last trial
medication. At the same time, male subjects with reproductive potential must refrain
from sperm donation from signing their informed consent until six months after the
last trial medication.
Exclusion Criteria:
1. Subjects previously treated with other CDK9 inhibitors;
2. Subjects who are allergic to the active ingredients and/or excipients of the
investigational drugs (QHRD107, Veneckla, and azacytidine);
3. Subjects with a history of myeloproliferative tumors (MPN);
4. Subjects with a history of chronic myeloid leukemia (CML);
5. Subjects with Ph chromosome-positive or BCR-ABL fusion gene positive acute myeloid
leukemia (AML);
6. Confirmed acute promyelocytic leukemia;
7. Patients with AML central nervous system infiltration;
8. Subjects with extramedullary leukemia (such as myeloid sarcoma, skin infiltration,
etc.) (except extramedullary lesions such as liver, spleen, and lymph node
involvement);
9. Human immunodeficiency virus (HIV) antibody positive subjects; Subjects with active
HBV infection: hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb) positive, and peripheral blood hepatitis B virus (HBV-DNA) higher than the
upper limit of normal; Subjects with active HCV infection: HCV antibody positive,
peripheral blood HCV RNA positive;
10. The subject has an active infection (including bacterial, viral, and fungal
infections) that requires systemic antibiotic treatment as determined by the
investigator to be clinically significant;
11. People with significant active cardiovascular disease within the previous 6 months,
including but not limited to: ≥III Heart failure as defined by the New York Heart
Association (NYHA); Angina pectoris requiring surgical treatment, unstable angina
pectoris, myocardial infarction; Hypertension that remains poorly controlled after
treatment (i.e., systolic ≥160 mmHg, diastolic ≥90 mmHg); Uncontrolled arrhythmias;
The left ventricular function resting ejection fraction measured by echocardiography
was less than 50%. QT interval: > 450 ms for men and > 470 ms for women (according
to the QTcF formula), or are on medication known to lengthen the QT/QTc interval, or
have other factors that may lengthen the QTc interval; Or for patients whose QT
interval is still > 450 ms after QT interval prolongation treatment;
12. Patients who have received allogeneic hematopoietic stem cell transplantation within
60 days of their initial investigational treatment must discontinue all
immunosuppressants during the investigational treatment;
13. Patients who have previously received CAR-T therapy;
14. The subject has a malabsorption syndrome or other comorbid condition that prevents
him from swallowing the capsule or administering the drug through enteral channels;
15. A history of other malignancies in the past 5 years, excluding cured basal cell
carcinoma of the skin, localized squamous cell carcinoma of the skin, carcinoma in
situ of the cervix, or carcinoma in situ of the breast;
16. Pregnant or lactating women, or subjects who are fertile and do not want to take
effective contraceptive measures;
17. Any ill-controlled clinical problems (such as severe psychiatric, neurological,
cardiovascular, respiratory, digestive, urinary, etc.) or other factors that the
investigator believes prevented the subject from completing the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Zip:
450000
Country:
China
Status:
Recruiting
Contact:
Last name:
Wu Jilian, doctor
Phone:
400-0371-818
Email:
jleewu@163.com
Investigator:
Last name:
Zhang Yanli, Doctor
Email:
Principal Investigator
Facility:
Name:
The First People's Hospital of Changzhou
Address:
City:
Changzhou
Zip:
213000
Country:
China
Status:
Recruiting
Contact:
Last name:
Li Jie, doctor
Phone:
0519-68870885
Email:
czyygcp@czfph.com
Investigator:
Last name:
Gu Weiying, doctor
Email:
Principal Investigator
Facility:
Name:
Huai 'an First People's Hospital
Address:
City:
Huaian
Zip:
223300
Country:
China
Status:
Recruiting
Contact:
Last name:
Liu Yanfei, Doctor
Phone:
0517-80872519
Email:
hayyyw@qq.com
Investigator:
Last name:
Wang Chunling, Doctor
Email:
Principal Investigator
Facility:
Name:
Zhongda Hospital
Address:
City:
Nanjing
Zip:
210009
Country:
China
Status:
Recruiting
Contact:
Last name:
Yang Yue, bachelor
Phone:
025-83272084
Email:
whp57@163.com
Investigator:
Last name:
Ge Zheng, Doctor
Email:
Principal Investigator
Facility:
Name:
Jiangsu Province Hospital
Address:
City:
Nanjing
Zip:
210036
Country:
China
Status:
Recruiting
Contact:
Last name:
Chai Yi, doctor
Phone:
025-68306259
Email:
littlechaiyi@163.com
Investigator:
Last name:
Qian Sixuan, Doctor
Email:
Principal Investigator
Facility:
Name:
ShengJing Hospital
Address:
City:
Shenyang
Zip:
110004
Country:
China
Status:
Recruiting
Contact:
Last name:
Li Hui, doctor
Phone:
024-96615-71146
Email:
lih@sj-hospital.org
Investigator:
Last name:
Yang Wei, doctor
Email:
Principal Investigator
Facility:
Name:
Qilu Hospital of Shandong University
Address:
City:
Jinan
Zip:
250000
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhao shiliang, doctor
Phone:
0531-82165412
Email:
zhaoshiliang208@163.com
Investigator:
Last name:
Ji Min, doctor
Email:
Sub-Investigator
Facility:
Name:
Tongren Hospital Shanghai Jiao Tong University School Of Medicine
Address:
City:
Shanghai
Zip:
200000
Country:
China
Status:
Recruiting
Contact:
Last name:
Gan Yuan, bachelor
Phone:
021-52039999021-52039999-6310
Email:
gcpjgb@163.com
Investigator:
Last name:
Liu Ligen, doctor
Email:
Principal Investigator
Facility:
Name:
Ruijin hospitol
Address:
City:
Shanghai
Zip:
200025
Country:
China
Status:
Recruiting
Contact:
Last name:
WU Jiajie, bachelor
Phone:
021-64370045
Phone ext:
675205
Email:
ruijin_gcp@126.com
Facility:
Name:
Zhongnan Hospital of Wuhan University
Address:
City:
Wuhan
Zip:
430000
Country:
China
Status:
Recruiting
Contact:
Last name:
Chen Bo, doctor
Phone:
027-67813097
Email:
znyysysm@126.com
Investigator:
Last name:
Zhou Fuling, doctor
Email:
Principal Investigator
Start date:
August 10, 2023
Completion date:
May 10, 2025
Lead sponsor:
Agency:
Changzhou Qianhong Bio-pharma Co., Ltd.
Agency class:
Industry
Source:
Changzhou Qianhong Bio-pharma Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06532058
