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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)

ConditionsAcute Myeloid LeukemiaTP53
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMasonic Cancer Center, University of Minnesota

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • Bortezomib

    Drug

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

  • CPX-351

    Drug

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

Treatment groups

32 Participants
are divided into 5 treatment groups
Group A: Phase 1: Dose Level -1Experimental treatment 2 interventions
Group B: Phase 1: Dose Level 2Experimental treatment 2 interventions
Group C: Phase 1: Dose Level 3Experimental treatment 2 interventions
Group D: Phase 1: Dose Level 4Experimental treatment 2 interventions
Group E: Phase 2Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Percentage of Participants with Complete Response

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

Time frame
2 years
2

Determine Maximum Tolerated Dose

Time frame
1 year

Secondary outcomes

1

Determine Overall Response Rate

Evaluate ORR (CR+CRi) after treatment

Time frame
2 years
2

Average rate of allo-HCT among participants

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

Time frame
2 years
3

Overall Survival

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

Time frame
1 year
4

Overall Survival

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

Time frame
2 year

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Masonic Cancer Center, University of Minnesota

Lead sponsor

Source ClinicalTrials.gov
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