Acute Myeloid LeukemiaPhase 1/2NCT07008638
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)
A Phase 1/2 study testing Bortezomib and CPX-351 in people with Acute Myeloid Leukemia and TP53, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, TP53
- What is being tested?
- Bortezomib and CPX-351
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jul 2025to 27 Jan 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- Received systemic chemotherapy for the treatment of AML
- Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Masonic Cancer Center
Minneapolis, Minnesota, 55455
Joseph Norton, DO, (612) 626-3107, norto491@umn.edu
About this study
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)
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.
- Conditions
- Acute Myeloid Leukemia, TP53
- Being tested
- Bortezomib, CPX-351
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Bortezomib at assigned study dose in mg/m2 will be given subcutaneously on days 1, 4, 8, and 11
CPX-351Drug
Also called Liposomal daunorubicin, Cytarabine
CPX-351 given intravenously on day 1, 3, and 5
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Dose Level -1 | Experimental | Bortezomib 0.7mg/m2 in combination with CPX-351 Receives: Drug: Bortezomib; Drug: CPX-351 |
| Phase 1: Dose Level 2 | Experimental | Bortezomib 1mg/m2 in combination with CPX-351 Receives: Drug: Bortezomib; Drug: CPX-351 |
| Phase 1: Dose Level 3 | Experimental | Bortezomib 1.3 mg/m2 in combination with CPX-351 Receives: Drug: Bortezomib; Drug: CPX-351 |
| Phase 1: Dose Level 4 | Experimental | Bortezomib 1.5 mg/m2 in combination with CPX-351 Receives: Drug: Bortezomib; Drug: CPX-351 |
| Phase 2 | Experimental | Maximum tolerated dose of Bortezomib in combination with CPX-351 Receives: Drug: Bortezomib; Drug: CPX-351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Complete Response
To evaluate the CR rate of bortezomib + CPX-351 for the treatment of TP53m AML.
Measured: 2 years
Determine Maximum Tolerated Dose
Measured: 1 year
Secondary outcomes (5)
Determine Overall Response Rate
Evaluate ORR (CR+CRi) after treatment
Measured: 2 years
Average rate of allo-HCT among participants
Evaluate the rate of allo-HCT within 2 years among patients who received treatment
Measured: 2 years
Overall Survival
estimate 1-year and 2-year OS, defined as the time from cohort assignment to death from any cause
Measured: 1 year
Overall Survival
estimate 1-year and 2-year OS, defined as the time from cohort assignment to death from any cause
Measured: 2 year
Average time to relapse
- To estimate time to relapse, defined as the time from cohort assignment to disease recurrence
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2025
- Study start7 Jul 2025
- Primary completion30 Dec 2027 (estimated)
- Study completion27 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07008638
- Sponsor's protocol ID
- 2024LS157
- Status last verified
- Oct 2026
- First submitted
- 29 May 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No