Overview

Eligibility

Design Details

Arms & Interventions

Outcome Measures

Trial Sites

Source: NCT07008638

Recruiting

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)

Interventional

Phase 1/2

Masonic Cancer Center

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.

Treatment Category

Other Drugs

Required Mutations

None

Trial Started

2025-07-07

Last Updated by Sponsor

2025-07-09

Estimated Completion

2027-12-30

Eligibility

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

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Design Details

AllocationNon-Randomized

Intervention ModelSequential Assignment

MaskingNone (Open Label)

Number to Enroll32

Arms & Interventions

Arms

Interventions

Type: Experimental

Description: Bortezomib 0.7mg/m2 in combination with CPX-351

Interventions:

Bortezomib
CPX-351

Outcome Measures

Primary Outcome Measures

Percentage of Participants with Complete Response2 years

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

Determine Maximum Tolerated Dose1 year

Secondary Outcome Measures

Determine Overall Response Rate2 years

Evaluate ORR (CR+CRi) after treatment

Average rate of allo-HCT among participants2 years

Evaluate the rate of allo-HCT within 2 years among patients who received treatment

Overall Survival1 year

estimate 1-year and 2-year OS, defined as the time from cohort assignment to death from any cause

Overall Survival2 year

estimate 1-year and 2-year OS, defined as the time from cohort assignment to death from any cause

Average time to relapse2 year

• To estimate time to relapse, defined as the time from cohort assignment to disease recurrence