Bortezomib combined with CPX-351 for newly diagnosed TP53‑mutated acute myeloid leukemia
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 trial tests whether adding the proteasome inhibitor bortezomib to CPX‑351 helps adults with newly diagnosed TP53‑mutated AML tolerate treatment and improve remission and survival.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 32 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Masonic Cancer Center, University of Minnesota Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Minneapolis, Minnesota) |
| Trial ID | NCT07008638 on ClinicalTrials.gov |
What this trial studies
This Phase I/II trial gives adults with newly diagnosed TP53‑mutated AML a combination of bortezomib (a proteasome inhibitor) and CPX‑351 (liposomal daunorubicin and cytarabine) to define safety and look for early signs of benefit. Phase I uses dose escalation to determine tolerability and a recommended dose, while Phase II measures preliminary efficacy outcomes such as complete remission, minimal residual disease status, and overall response rate. Secondary endpoints include rate of proceeding to allogeneic hematopoietic cell transplant, treatment‑related mortality, overall survival, and disease‑free survival at one and two years. All outcome assessments are performed alongside standard‑of‑care AML management at the sponsor site.
Who should consider this trial
Good fit: Adults (≥18 years) with newly diagnosed TP53‑mutated AML who have not received systemic chemotherapy, have Karnofsky performance status ≥70, and meet the study's organ function and contraceptive requirements.
Not a fit: Patients with prior systemic AML chemotherapy, significant organ dysfunction, poor performance status, or without a TP53 mutation are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the combination could increase remission rates and enable more patients with TP53‑mutated AML to reach transplant and live longer.
How similar studies have performed: CPX‑351 has shown benefit in certain secondary or therapy‑related AML settings and bortezomib has limited prior AML data, but combining them specifically for TP53‑mutated AML is relatively novel with limited direct clinical evidence.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Minneapolis, Minnesota
- Masonic Cancer Center — Minneapolis, Minnesota, United States (Recruiting)
Study contacts
- Study coordinator: Joseph Norton, DO
- Email: norto491@umn.edu
- Phone: (612) 626-3107
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.