Recruiting
Phase 1
Phase 2

Bortezomib & CPX-351

Sponsor:

Masonic Cancer Center, University of Minnesota

Code:

NCT07008638

Conditions

Acute Myeloid Leukemia

TP53

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Bortezomib

CPX-351

Study Details

Brief 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).

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

Study ID

NCT07008638

Start date

Jul 7, 2025

Status verified date

Jul, 2026

Completion date

Jan 27, 2028

Anticipated

Primary completion date

Dec 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

32 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1: Dose Level -1

Bortezomib 0.7mg/m2 in combination with CPX-351

experimental: Phase 1: Dose Level 2

Bortezomib 1mg/m2 in combination with CPX-351

experimental: Phase 1: Dose Level 3

Bortezomib 1.3 mg/m2 in combination with CPX-351

experimental: Phase 1: Dose Level 4

Bortezomib 1.5 mg/m2 in combination with CPX-351

experimental: Phase 2

Maximum tolerated dose of Bortezomib in combination with CPX-351

Interventions

Bortezomib

Bortezomib at assigned study dose in mg/m2 will be given subcutaneously on days 1, 4, 8, and 11

CPX-351

CPX-351 given intravenously on day 1, 3, and 5

Primary outcome measure

  • Percentage of Participants with Complete Response [ Time Frame: 2 years ]
  • Determine Maximum Tolerated Dose [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Joseph Norton, DO

(612) 626-3107norto491@umn.edu

Zohar Sachs, MD, PhD

612-626-7055sachs038@umn.edu

Locations

Masonic Cancer Center

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Joseph Norton, DO

(612) 626-3107norto491@umn.edu

More Information

Sponsor

Masonic Cancer Center, University of Minnesota

Last update posted

Jul 22, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota on 2026-07-22.