A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LP-108, a BCL-2 Inhibitor, Combined With Azacitidine In Subjects With AML, MDS, CMML
Status: Recruiting
Location: See all (3) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY
This is a Phase 1, open-label, multicenter, dose-escalation \& expansion study to evaluate the safety,tolerability and pharmacokinetics (PK) of LP-108, a BCL-2 inhibitor, combined with azacitidine, to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RP2D), and to assess the preliminary efficacy of this combination.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:
• Subject must has a diagnosis of one of the following: relapsed or refractory (R/R) or untreated ineligible for treatment with a standard induction chemotherapy acute myeloid leukemia (AML) ; R/R myelodysplastic syndrome(MDS) or untreated MDS with excess blasts defined as ≥ 5% blasts in either bone marrow or blood or with high risk (high and very high-risk groups according to IPSS-R) ;CMML-1 or 2 by WHO, no requirements for prior therapy.
• ECOG performance status ≤ 2.
• Estimated survival ≥ 12 weeks.
• Baseline white blood cell count (WBC) ≤ 25 x 109/L.
• Subject must has adequate organ function as defined below: Aspartate transaminase (AST) and alanine transaminase (ALT)≤3 x ULN; Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin); adequate renal function as demonstrated by a creatinine clearance ≤1.5 x ULN ; calculated by the Cockcroft Gault formula; APTT ≤ 1.5 x ULN, INR ≤ 1.5 x ULN.
• Prior treatment-related toxicities must be grade 1 or baseline except for alopecia.
• If subject is sexually active, he/she must agree to carry out birth control throughout the study and 90 days after the last dose of LP-108. Subject must agree to have a negative serum β-HCG test result within 7 days prior to study drug.
• Subject must voluntarily sign and date an informed consent.
Locations
Other Locations
China
The First Affiliated Hospital of Nanchang University
RECRUITING
Nanchang
First Affiliated Hospital of Soochow University
RECRUITING
Suzhou
Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital
RECRUITING
Zhengzhou
Contact Information
Primary
Yue Shen, PhD
yshen@lupengbio.com
86-020-31605119
Time Frame
Start Date:2023-02-14
Estimated Completion Date:2025-12-31
Participants
Target number of participants:198
Treatments
Experimental: Dose Escalation
LP-108: Cycle 0: ramp-up from Day 1, Cycle 1+: at escalating dose levels in participants with AML, MDS or CMML.~Azacitidine: beginning on Day 1 through Day 7 of each Cycle (expect for Cycle 0).~Strong/moderate CYP3A inhibitor and inducer are prohibited. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Experimental: Safety Expansion
LP-108: Cycle 0: ramp-up from Day 1, Cycle 1+: Participants with AML, MDS or CMML will be treated with LP-108 to enable selection of the recommended Phase 2 dose (RP2D).~Azacitidine: beginning on Day 1 through Day 7 of each Cycle (expect for Cycle 0).~Strong/moderate CYP3A inhibitor and inducer are prohibited. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Experimental: Efficacy Expansion [AML]
LP-108: Cycle 0: ramp-up from Day 1, Cycle 1+: at RP2D level in participants with AML .~Azacitidine: beginning on Day 1 through Day 7 of each Cycle (expect for Cycle 0).~After the completion of Part 1, the Part 2 dose expansion phase will begin. Strong/moderate CYP3A inhibitor and inducer are prohibited. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Experimental: Efficacy Expansion [MDS&CMML]
LP-108: Cycle 0: ramp-up, Cycle 1+: at RP2D level in participants with MDS or CMML.~Azacitidine: beginning on Day 1 through Day 7 of each Cycle (expect for Cycle 0).~Strong/moderate CYP3A inhibitor and inducer are prohibited. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.