Trial Title:
A Study to Assess Safety and Preliminary Efficacy of LP-108 Combined With Azacitidine In Subjects With AML, MDS, CMML
NCT ID:
NCT05641259
Condition:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Azacitidine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This is a Phase 1 study with a dose escalation design and an expansion cohort.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LP-108
Description:
Oral administration for 21 or 28 days on a 28-day cycle
Arm group label:
Dose Escalation
Arm group label:
Efficacy Expansion [AML]
Arm group label:
Efficacy Expansion [MDS&CMML]
Arm group label:
Safety Expansion
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Subcutaneous administration for 7 days on a 28-day cycle at the dose of 75mg/m2 2-2.5h
hours after LP-108.
Arm group label:
Dose Escalation
Arm group label:
Efficacy Expansion [AML]
Arm group label:
Efficacy Expansion [MDS&CMML]
Arm group label:
Safety Expansion
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.
Detailed description:
This Phase 1 study will look at different doses and different treatment schedules in
order to better understand the effects of the combined regimens on the newly diagnosed or
refractory/relapsed adult participants with AML ,MDS or CMML. The procedures include
screening for eligibility, study treatments, and blood & bone marrow tests. All the
safety events will be record, pharmacokinetic parameters (Tmax, Cmax,T1/2, AUC et al.)
will be calculated, response and survival will be assess during the study. Participants
will be treated indefinitely until disease progression, unacceptable toxicity or
withdrawal for other reasons.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Subject is allergic to LP-108, Azacitidine or excipients, or with poor tolerance to
Azacitidine.
- Subject has received prior therapy with a BH3 mimetic.
- Subject has acute promyelocytic leukemia.
- Subject has t(9;22) karyotype abnormality or positive BCR/ABL1 fusion gene.
- Subject has known and active CNS involvement.
- Subject has myeloid sarcoma but no bone marrow involvement.
- Subject has Acute unidentified leukemia.
- Subject has treatment related MDS or AML.
- Subject has AML/MDS/CMML with myelofibrosis ≥ grade 2.
- Subject has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or
autologous HSCT within 3 months prior to the first dose of study drug.
- Subject must be at least 4 weeks from antitumor therapy, major surgery, radiation
therapy, or participation in other investigational trials.
- Subject has received a strong and/or moderate CYP3A inhibitor or inducer, P-gp
inhibitor or CYP2C8 substrate within 14 days prior to the initiation of study
treatment.
- Subject has received drugs with a potential to cause prolonged QT intervals or
torsade de pointes.
- Administration or consumption of any of the following within 3 days prior to the
first dose of study drug: Grapefruit or grapefruit products; Seville oranges
(including marmalade containing Seville oranges); Star fruit.
- Subject has known malignancy within 3 years prior to the first dose of study drug,
with the exception of: Adequately treated basal skin cancers, in situ carcinoma of
the cervix uteri or breast, localized squamous cell carcinoma.
- Subject has serious and/or uncontrolled systemic diseases, in the opinion of the
investigator, the subject is inappropriate for enrollment into this study (serious
active infection with grade ≥ 2(based on CTCAE), high blood pressure that cannot be
controlled by medication, diabetes, unstable angina, congestive heart failure,
Respiratory diseases requiring continuous oxygen intake, severe vascular embolism,
uncontrolled massive bleeding or bleeding from vital organs, severe liver, kidney or
metabolic diseases, such as cirrhosis, kidney failure, etc.).
- Subject has myocardial infarction or stroke within 6 months prior to the first dose
of study drug.
- Subject has a cardiac history including the following: History of CHF requiring
treatment or Ejection Fraction <50% or a cardiovascular disability status of New
York Heart Association.
- Subject has uncontrolled and/or active systemic infection (viral, bacterial or
fungal).
- Subject has difficulty to swallow pills or has conditions that affect drug
absorption or pharmacokinetics.
- Strong and/or moderate CYP3A inhibitor or inducer and CYP2C8 substrate cannot be
discontinued during the study.
- Vaccination with live, attenuated vaccines ≤4 weeks prior to initiation of study
treatment or anticipation of need for such a vaccine during the study or 4 weeks
after the last dose of study drug.
- Subject has an autoimmune disease that requires immunosuppressive therapy In the
opinion of the investigator, the subject is inappropriate for enrollment into this
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Country:
China
Status:
Recruiting
Contact:
Last name:
Fei Li
Facility:
Name:
First Affiliated Hospital of Soochow University
Address:
City:
Suzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Depei Wu
Facility:
Name:
Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital
Address:
City:
Zhengzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Fei Li
Start date:
February 14, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Guangzhou Lupeng Pharmaceutical Company LTD.
Agency class:
Industry
Source:
Guangzhou Lupeng Pharmaceutical Company LTD.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05641259
