A Study of GFH009 in Patients With Hematologic Malignancies

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

GFH009 is a potent and highly selective CDK9 inhibitor. The study consists of a dose escalation and a dose expansion part. The purpose of this study is to investigate the safety and tolerability of GFH009 in relapsed/refractory hematologic malignancies [acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and lymphoma], will also explore the preliminary anti-tumor activities of GFH009 in the studied population.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd; Zhejiang Genfleet Therapeutics Co., Ltd.

Criteria

Inclusion Criteria

1. Patients with cytological or histologically confirmed relapsed or refractory hematologic malignancies (AML, CLL/SLL and lymphoma)

2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubin is < 1.5 × ULN.

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 × ULN.

3. Amylase and lipase ≤1.5 × ULN

4. Electrolytes and uric acid levels within normal limits (WNL) or correctable with medical intervention

5. For women of childbearing potential, must consent to use two highly effective methods (i.e, total abstinence, placement of an intrauterine device) of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug; Men with a partner of childbearing potential, must consent to use two highly effective methods of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug.

Exclusion Criteria

1. Patients with bulky disease who require cytoreductive therapy.

2. Symptomatic central nervous system metastases or primary lymphoma such as primary CNS lymphoma, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS-directed therapy and are on a stable or decreasing dose of corticosteroids are eligible for study entry.

3. Severe cardiovascular disease within 6 months of study entry, including any of the following:

• Clinically significant heart disease such as congestive heart failure requiring treatment (NYHA class III or IV), LVEF < 45% as determined by MUGA scan or echocardiogram (ECHO), (if just with historical occasional low LVEF but without any symptoms or relevant medical history, and the LVEF at screening is > 45%, the subject is eligible), or clinically significant arrythmia.

• History/evidence of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting).

• QTcF ≥ 450 msec on screening ECG.

4. Concurrent malignancy within 5 years (for AML patients, 2 years) prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment, ductal carcinoma in situ of the breast, and superficial non-muscle invasive urothelial carcinoma (excluding T1 lesions and CIS).

5. Chronic or active hepatitis B or hepatitis C virus infection.

6. History of HIV infection.

7. Concomitant medications that are strong CYP3A4 inhibitors and strong inducers within 7 days of first dose. Avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pomelos, star citrus fruits or St. John's wort within 7 days of first dose.

8. Medications that are known to prolong the QT interval are prohibited on this study.