Phase I/II Clinical Trial of Proteasome Inhibitor in Combination With CPX-351 for the Treatment of Newly-Diagnosed TP53-mutated Acute Myeloid Leukemia (AML)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Bortezomib, CPX-351.
- Who it may be relevant to
- Registry conditions: Acute Myeloid Leukemia, TP53. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
HM2024-29: Phase I/II Clinical Trial of Proteasome Inhibitor in Combination With CPX-351 for the Treatment of Newly-Diagnosed TP53-mutated Acute Myeloid Leukemia (AML)
Overview
This is a Phase I/II study evaluating safety and efficacy of proteasome inhibitor (bortezomib) in combination with CPX-351 (liposomal daunorubicin and cytarabine) for the treatment of newly-diagnosed TP53-mutated acute myeloid leukemia (TP53m AML). The primary endpoint of the study is to define safety/tolerability (phase I) and preliminary efficacy profile (phase II) of the treatment. The secondary endpoints of interest are complete remission (CR) rate, detectable minimal residual disease (MRD) status, overall response rate (ORR), rate of allogeneic hematopoietic cell transplantation (allo-HCT), treatment-related mortality (TRM), overall survival (OS), achievement of complete remission anytime in 1 year, and disease-free survival (DFS) at 1 year and 2 years. All the patient outcomes assessments will be performed as part of standard-of-care AML management. The hypothesis is the combination of bortezomib and CPX-351 will have an acceptable safety profile in this patient population based on the data from previous studies. The treatment will attenuate Nuclear Factor kB pathway activation in these cells and eradicate TP53m leukemia stem cells (LSC) leading to increased response rate and survival in these patients.
Interventions
- Drug Bortezomib
Bortezomib at assigned study dose in mg/m2 will be given subcutaneously on days 1, 4, 8, and 11 - Drug CPX-351
CPX-351 given intravenously on day 1, 3, and 5
Primary outcome measures
- Percentage of Participants with Complete Response [Time frame: 2 years]
- Determine Maximum Tolerated Dose [Time frame: 1 year]
Secondary outcome measures (5)
- Determine Overall Response Rate [Time frame: 2 years]
- Average rate of allo-HCT among participants [Time frame: 2 years]
- Overall Survival [Time frame: 1 year]
- Overall Survival [Time frame: 2 year]
- Average time to relapse [Time frame: 2 year]
Eligibility criteria
Inclusion criteria
- Adult (age ≥ 18 years at time of consent)
- Have not received any systemic chemotherapy for the treatment of AML. Use of hydroxyurea and leukapheresis to control excess peripheral blasts is permissible. WBC < 25,000 to initiate bortezomib, must reach this threshold by day 7 of CPX-351.
- Karnofsky performance status (KPS) ≥ 70
- Adequate renal, hepatic and cardiac function defined as
- Renal: An estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2
- Hepatic: AST and ALT ≤3 x ULN, ALP ≤2.5 x ULN, and total bilirubin ≤1.5 x ULN. (exception for Gilbert's syndrome or leukemic infiltration of liver)
- Cardiac: New York Heart Association (NYHA) Class I or II, left ventricular ejection fraction > 50% by echocardiogram, MUGA or cardiac MRI
- Sexually active couples of childbearing potential must agree to use effective contraception or abstinence during treatment and for at least 7 months after the final dose of study drug
- Provides voluntary written consent before the performance of any study related activities not part of standard of care.
Exclusion criteria
- Received systemic chemotherapy for the treatment of AML
- Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia
- Active central nervous system malignancy or symptoms of CNS involvement
- Symptomatic extramedullary disease
- Known history of uncontrolled HIV or active hepatitis B or active hepatitis C infection
- Has any of the following cardiac abnormalities
- Symptomatic congestive heart failure
- Myocardial infarction less than or equal to 6 months prior to enrollment
- Unstable angina pectoris
- Serious uncontrolled cardiac arrhythmia
- Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Potential participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis
- Participants for whom administration of CPX-351 would exceed their lifetime cumulative daunorubicin exposure limit of 550 mg/m2 (or 400 mg/m2 in patients with prior chest radiation) or equivalent anthracycline dose.
- Pregnant or breastfeeding, or planning pregnancy within 3 months after the treatment completion
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Masonic Cancer Center — Minneapolis
Identifiers
NCT: NCT07008638 · 2024LS157