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)

NCT07008638 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2024LS157
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Complete Response

  To evaluate the CR rate of bortezomib + CPX-351 for the treatment of TP53m AML.

  2 years

• Determine Maximum Tolerated Dose

  1 year

Secondary Outcomes (5)

• Determine Overall Response Rate

  2 years

• Average rate of allo-HCT among participants

  2 years

• Overall Survival

  1 year

• Overall Survival

  2 year

• Average time to relapse

  2 year

Study Arms (5)

Phase 1: Dose Level -1

EXPERIMENTAL

Bortezomib 0.7mg/m2 in combination with CPX-351

Drug: Bortezomib; Drug: CPX-351

Phase 1: Dose Level 2

EXPERIMENTAL

Bortezomib 1mg/m2 in combination with CPX-351

Drug: Bortezomib; Drug: CPX-351

Phase 1: Dose Level 3

EXPERIMENTAL

Bortezomib 1.3 mg/m2 in combination with CPX-351

Drug: Bortezomib; Drug: CPX-351

Phase 1: Dose Level 4

EXPERIMENTAL

Bortezomib 1.5 mg/m2 in combination with CPX-351

Drug: Bortezomib; Drug: CPX-351

Phase 2

EXPERIMENTAL

Maximum tolerated dose of Bortezomib in combination with CPX-351

Drug: Bortezomib; Drug: CPX-351

Interventions

Bortezomib DRUG

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

Phase 1: Dose Level -1; Phase 1: Dose Level 2; Phase 1: Dose Level 3; Phase 1: Dose Level 4; Phase 2

CPX-351 DRUG

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

Also known as: Liposomal daunorubicin, Cytarabine

Phase 1: Dose Level -1; Phase 1: Dose Level 2; Phase 1: Dose Level 3; Phase 1: Dose Level 4; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Bortezomib; CPX-351; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Joseph Norton, DO

CONTACT

(612) 626-3107; norto491@umn.edu

Zohar Sachs, MD, PhD

CONTACT

612-626-7055; sachs038@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: June 6, 2025
• Study Start: July 7, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): January 27, 2028
• Last Updated: July 9, 2025

Record last verified: 2025-07

Locations

US (1)