Phase IIa Study to Assess Safety and Efficacy in the Relapsed/Refractory Acute Myeloid Leukemia

NCT06532058 | Recruiting Phase 2

• 1 other identifier: QH-RD107-02-01
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 10

Brief 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

Conditions

Relapsed/Refractory Acute Myeloid Leukemia (R/R-AML)

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose（Dose Escalation Phase）

  Enrolled subjects performed dose climbing according to the "3+3 principle".The highest dose of DLT（Dose-Limiting Toxicity） incidence 1/6 is MTD

  From screenng through to 28 day follow up period

• The Compound complete response rate (CCR) and the corresponding mitigation duration (DORccr)（Dose expansion phase）

  The Compound complete response rate (CCR) was defined as the percentage of participants who achieved complete remission(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery (CRi) per the European LeukemiaNet (ELN) recommendations for AML. CR was defined as bone marrow blasts \< 5%, absence of circulating blasts,absence of extramedullary disease,ANC ≥ 1.0 × 10˄9/L (1,000/µL),platelet count ≥ 100 × 10˄9/L (100 000/µL).CRh was defined as ANC ≥ 0.5 × 10˄9/L (500/µL) and platelet count ≥ 50 × 10˄9/L (50000/µL), otherwise all other CR criteria met.CRi was defined as all CR criteria except for residual neutropenia \< 1.0 × 10˄9/L (1,000/µL) or thrombocytopenia \< 100 × 10˄9/L (100 000/µL).DORccr refers to the time between the first assessment of efficacy reaching CR/CRi/CRh/MLFS/PR and the first assessment of disease recurrence or death from any cause.

  From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）

Secondary Outcomes (9)

• Safety as assessed by incidence ,severity,and causality of adverse events

  From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）

• Plasma measurements of QHRD107

  At the end of Cycle 1 (each cycle is 28 days)

• Complete Remission Rate

  From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）

• Objective Remission Rate

  From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）

• Duration of Remission(DOR)

  From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）

Study Arms (2)

Part-A (Cohort 1-3)

EXPERIMENTAL

Three dose groups were set up. The doses of QHRD107 capsules were 40 mg Q12H, 60 mg Q12H and 80 mg Q12H, respectively, combined with Venclexta and Azacitidine.

Drug: QHRD107 capsule，Venclexta and Azacitidine

Part-B (Cohort 1-2)

EXPERIMENTAL

Cohort 1： \[QHRD107 capsule 60mg Q12H D1-28\]+\[Venclexta QD D1-28\]+\[Azacitidine QD D1-7\]; Cohort 1：\[QHRD107 capsule 80mg Q12H D1-28\]+\[Venclexta QD D1-28\]+\[Azacitidine QD D1-7\] .

Drug: QHRD107 capsule，Venclexta and Azacitidine

Interventions

QHRD107 capsule，Venclexta and Azacitidine DRUG

QHRD107（orally），Venclexta（orally），Azacitidine（subcutaneous injection）

Also known as: CDK9 inhibitors

Part-A (Cohort 1-3); Part-B (Cohort 1-2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign informed consent;
• Age 18 and above;
• 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:
• Initial treatment cases that failed after 2 courses of treatment with standard protocols;
• Relapse within 12 months after complete remission (CR) after consolidation and intensive treatment;
• Recurrence after 12 months but failed to respond to conventional chemotherapy;
• Two or more relapses.
• ECOG evaluation ≤2 points;
• Expected survival ≥3 months;
• White blood cell (WBC) count \<25×109 cells /L (hydroxyurea is allowed to control the white blood cell count before treatment);
• 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;
• Subjects must have adequate renal function: creatinine clearance ≥50 mL/min (calculated using the Cockroft-Gault formula);
• 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;

You may not qualify if:

• Subjects previously treated with other CDK9 inhibitors;
• Subjects who are allergic to the active ingredients and/or excipients of the investigational drugs (QHRD107, Veneckla, and azacytidine);
• Subjects with a history of myeloproliferative tumors (MPN);
• Subjects with a history of chronic myeloid leukemia (CML);
• Subjects with Ph chromosome-positive or BCR-ABL fusion gene positive acute myeloid leukemia (AML);
• Confirmed acute promyelocytic leukemia;
• Patients with AML central nervous system infiltration;
• Subjects with extramedullary leukemia (such as myeloid sarcoma, skin infiltration, etc.) (except extramedullary lesions such as liver, spleen, and lymph node involvement);
• 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;
• 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;
• 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;
• 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;
• Patients who have previously received CAR-T therapy;
• The subject has a malabsorption syndrome or other comorbid condition that prevents him from swallowing the capsule or administering the drug through enteral channels;
• 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;

Sponsors & Collaborators

• Changzhou Qianhong Bio-pharma Co., Ltd.: lead

Study Sites (10)

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430000, China

RECRUITING

The First People's Hospital of Changzhou

Changzhou, Jiangsu, 213000, China

RECRUITING

Huai 'an First People's Hospital

Huaian, Jiangsu, 223300, China

RECRUITING

Zhongda Hospital

Nanjing, Jiangsu, 210009, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210036, China

RECRUITING

ShengJing Hospital

Shenyang, Liaoning, 110004, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shangdong, 250000, China

RECRUITING

Tongren Hospital Shanghai Jiao Tong University School Of Medicine

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Ruijin hospitol

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Li Junmin, Doctor

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Junmin, Doctor

CONTACT

13817712211; lijunmin@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: a single-arm, open, multicenter Phase IIa study with dose escalation and dose extension

Study Record Dates

• First Submitted: July 20, 2024
• First Posted: August 1, 2024
• Study Start: August 10, 2023
• Primary Completion: February 10, 2025
• Study Completion: May 10, 2025
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)