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)

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Conditions

Acute Myeloid LeukemiaTP53

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2025-07-07
Study Completion:2028-01-27
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT07008638

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Adult (age ≥ 18 years at time of consent)
  2. * 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.
  3. * Karnofsky performance status (KPS) ≥ 70
  4. * Adequate renal, hepatic and cardiac function defined as
  5. * Renal: An estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2
  6. * 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)
  7. * Cardiac: New York Heart Association (NYHA) Class I or II, left ventricular ejection fraction \> 50% by echocardiogram, MUGA or cardiac MRI
  8. * 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
  9. * Provides voluntary written consent before the performance of any study related activities not part of standard of care.
  1. * Received systemic chemotherapy for the treatment of AML
  2. * Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia
  3. * Active central nervous system malignancy or symptoms of CNS involvement
  4. * Symptomatic extramedullary disease
  5. * Known history of uncontrolled HIV or active hepatitis B or active hepatitis C infection
  6. * Has any of the following cardiac abnormalities
  7. * Symptomatic congestive heart failure
  8. * Myocardial infarction less than or equal to 6 months prior to enrollment
  9. * Unstable angina pectoris
  10. * Serious uncontrolled cardiac arrhythmia
  11. * 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
  12. * 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.
  13. * Pregnant or breastfeeding, or planning pregnancy within 3 months after the treatment completion

Contacts and Locations

Study Contact

Joseph Norton, DO
CONTACT
(612) 626-3107
norto491@umn.edu
Zohar Sachs, MD, PhD
CONTACT
612-626-7055
sachs038@umn.edu

Study Locations (Sites)

Masonic Cancer Center
Minneapolis, Minnesota, 55455
United States

Collaborators and Investigators

Sponsor: Masonic Cancer Center, University of Minnesota

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-07
Study Completion Date2028-01-27

Study Record Updates

Study Start Date2025-07-07
Study Completion Date2028-01-27

Terms related to this study

Additional Relevant MeSH Terms

  • Acute Myeloid Leukemia
  • TP53