Palbociclib, all-trans retinoic acid and venetoclax for relapsed or refractory acute myeloid leukemia

Trial details

Who runs it

Second Affiliated Hospital of Nanchang University

Trial code

NCT07926607

Record updated

9 November 2026

Original description

This is a prospective, multicenter, single-arm, open-label Phase Ib/II clinical trial evaluating the safety, tolerability, and preliminary efficacy of palbociclib, all-trans retinoic acid (ATRA), and venetoclax (PAV regimen) in adult patients with relapsed or refractory acute myeloid leukemia (AML).Read full original descriptionShow less

A Phase Ib/II, Multicenter, Open-Label, Single-Arm Study of Palbociclib, All-Trans Retinoic Acid, and Venetoclax in Patients With Relapsed or Refractory Acute Myeloid Leukemia

This is a prospective, multicenter, single-arm, open-label Phase Ib/II clinical trial evaluating the safety, tolerability, and preliminary efficacy of palbociclib, all-trans retinoic acid (ATRA), and venetoclax (PAV regimen) in adult patients with relapsed or refractory acute myeloid leukemia (AML).

The Phase Ib portion will use a standard 3+3 dose-escalation design to evaluate dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD), and establish the recommended Phase II dose (RP2D). The Phase II portion will use Simon's two-stage design to further evaluate the antileukemic activity and safety of the combination regimen, with overall response rate (ORR) as the primary efficacy endpoint.

Additional assessments will include complete remission (CR), complete remission with incomplete hematologic recovery (CRi), measurable residual disease (MRD) negativity, event-free survival (EFS), overall survival (OS), and duration of response (DOR). Exploratory analyses will investigate treatment-associated changes in leukemic cell differentiation and apoptosis and identify potential biomarkers associated with treatment response.

**Inclusion Criteria:**; The participant or their legally authorized representative must provide written informed consent and be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures; Adults aged 18 years or older; Histologically, immunophenotypically, cytogenetically, or molecularly confirmed relapsed or refractory acute myeloid leukemia (R/R AML) according to WHO classification criteria. Relapsed or refractory AML is defined as failure to achieve remission after at least one cycle of standard induction therapy or recurrence of disease after achieving remission; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; Life expectancy greater than 3 months; Adequate organ function, defined as:; Total bilirubin ≤1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or ≤5 × ULN if the elevation is attributable to leukemic involvement; Creatinine clearance ≥30 mL/min; Left ventricular ejection fraction (LVEF) ≥50%; Corrected QT interval using Fridericia's formula (QTcF) ≤450 ms for males or ≤470 ms for females; White blood cell (WBC) count <25 × 10⁹/L before the first dose of study treatment. Cytoreduction with hydroxyurea or leukapheresis is permitted before treatment initiation; Women of childbearing potential must have a negative pregnancy test before enrollment. Male participants and women of childbearing potential must agree to use highly effective contraception during the study and for at least 6 months after the last dose of study treatment; **Exclusion Criteria:**; Acute promyelocytic leukemia (APL), characterized by t(15;17) translocation or positivity for the PML-RARα fusion gene; Active or symptomatic central nervous system leukemia; Use of strong CYP3A4 inhibitors (e.g., voriconazole or posaconazole) or strong CYP3A4 inducers (e.g., rifampin or carbamazepine) within 7 days before the first dose of study treatment when these medications cannot be replaced. Participants requiring strong CYP3A4 inhibitors for fungal infection prophylaxis or treatment may be enrolled if no suitable alternative is available, provided that palbociclib and venetoclax doses are adjusted according to the study protocol. However, strong CYP3A4 inhibitors are prohibited during venetoclax dose ramp-up; Previous treatment with venetoclax, another BCL-2 inhibitor, or a CDK4/6 inhibitor resulting in intolerable toxicity; Severe gastrointestinal disorders that may significantly impair oral drug absorption, such as Crohn's disease or severe ulcerative colitis, or inability to swallow oral tablets or capsules; Severe, active, and uncontrolled systemic infection, including bacterial, fungal, or viral infection; positive testing for human immunodeficiency virus (HIV); or active hepatitis B or hepatitis C infection; History of congenital or acquired long QT syndrome; current use of medications known to prolong the QT interval that cannot be discontinued (e.g., amiodarone, sotalol, or methadone); or myocardial infarction, unstable angina, severe arrhythmia, or New York Heart Association (NYHA) Class III-IV heart failure within the preceding 6 months; History of another malignancy, except for adequately treated nonmelanoma skin cancer, cervical carcinoma in situ, or similar conditions, with a disease-free interval of less than 2 years.

ClinicalTrials.gov NCT07926607