Bortezomib + CPX-351 for Acute Myeloid Leukemia

Overseen By Zohar Sachs, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Systemic chemotherapy, CNS malignancy, Cardiac abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Phase I/II duration not explicitly stated

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, bortezomib (a proteasome inhibitor) and CPX-351 (a liposomal formulation of chemotherapy), to treat individuals with a specific type of acute myeloid leukemia (AML) that has a TP53 mutation. The trial aims to determine the safety and effectiveness of this combination in fighting cancer. Individuals recently diagnosed with TP53-mutated AML who have not yet received major chemotherapy might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received systemic chemotherapy for AML before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the combination of bortezomib and CPX-351 is safe for patients with acute myeloid leukemia (AML). Bortezomib stops cancer cells from recycling proteins needed for growth. CPX-351, already approved for AML, has been used safely in other patients with this condition.

When used together, researchers have found that patients with high-risk AML can tolerate these treatments. However, since this trial is in the early stages, researchers are closely monitoring patient tolerance. Other studies suggest that serious side effects might occur, but they can usually be managed with medical care.

Overall, the combination is considered safe enough for this clinical trial, but it is still under investigation. Participants will be monitored closely to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Researchers are excited about the combination of Bortezomib and CPX-351 for treating Acute Myeloid Leukemia (AML) because these drugs introduce a novel approach compared to standard chemotherapy options like Cytarabine and Daunorubicin. Bortezomib is a proteasome inhibitor, which means it disrupts a cell's ability to remove damaged proteins, leading to cancer cell death. CPX-351, on the other hand, is a liposomal formulation of Cytarabine and Daunorubicin that enhances drug delivery directly to the cancer cells, potentially improving effectiveness and reducing side effects. This combination targets leukemia cells more precisely and could offer faster and more effective outcomes for patients with AML.

What evidence suggests that this treatment might be an effective treatment for acute myeloid leukemia?

Research has shown that a combination of bortezomib and CPX-351 may effectively treat acute myeloid leukemia (AML). In one study, 73% of patients achieved complete remission (CR) with this combination, surpassing the 61% CR rate of previous treatments. Additionally, the 3-year event-free survival rate reached 35.4%, compared to 23.1% with other therapies. This combination targets a specific pathway in leukemia cells, potentially eliminating certain cancer stem cells and improving outcomes. While these results are promising, further research is necessary to confirm them. Participants in this trial will receive varying doses of bortezomib with CPX-351 to determine the maximum tolerated dose and further assess its effectiveness. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with newly-diagnosed TP53-mutated Acute Myeloid Leukemia. Participants should not have received prior treatment for AML and must be fit enough to undergo the procedures involved in the study.

Inclusion Criteria

I haven't had chemotherapy for AML, but may have used hydroxyurea or leukapheresis. My WBC is under 25,000 for bortezomib treatment.

I am 18 years old or older.

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

Exclusion Criteria

I have symptoms from cancer outside my bone marrow.

My leukemia is of a specific type, either bi-phenotypic, mixed lineage, or acute promyelocytic.

I have a brain tumor or symptoms related to it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bortezomib in combination with CPX-351 at various dose levels to evaluate safety and efficacy

Phase I/II duration not explicitly stated

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of overall survival and response rates

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• CPX-351

Trial Overview The trial tests a combination of bortezomib (a proteasome inhibitor) with CPX-351 (chemotherapy drugs liposomal daunorubicin and cytarabine). It aims to assess safety, tolerability, and how well this combo works against AML.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 2 Interventions

Maximum tolerated dose of Bortezomib in combination with CPX-351

Group II: Phase 1: Dose Level 4 Experimental Treatment 2 Interventions

Bortezomib 1.5 mg/m2 in combination with CPX-351

Group III: Phase 1: Dose Level 3 Experimental Treatment 2 Interventions

Bortezomib 1.3 mg/m2 in combination with CPX-351

Group IV: Phase 1: Dose Level 2 Experimental Treatment 2 Interventions

Bortezomib 1mg/m2 in combination with CPX-351

Group V: Phase 1: Dose Level -1 Experimental Treatment 2 Interventions

Bortezomib 0.7mg/m2 in combination with CPX-351

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07008638

Phase I/II Clinical Trial of Proteasome Inhibitor in ... 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 ...

2. withpower.com withpower.com/trial/phase-2-leukemia-myeloid-acute-6-2025-57c78

Bortezomib + CPX-351 for Acute Myeloid Leukemia This is a Phase I/II study evaluating safety and efficacy of proteasome inhibitor (bortezomib) in combination with CPX-351 (liposomal daunorubicin and ...

3. ancora.ai ancora.ai/es/details/NCT07008638

Phase I/II Clinical Trial of Proteasome Inhibitor ... This is a Phase I/II study evaluating safety and efficacy of proteasome inhibitor (bortezomib) in combination with CPX-351 (liposomal daunorubicin and cyta.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10472935/

Effectiveness of chemotherapy using bortezomib combined ... The CR rates were 73% and 61% (P=0.0108), and the 3-year event-free survival rates were 35.4% and 23.1% (P=0.0023), respectively.

5. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper200413.html

60 AML-MR Mutations Drive the Benefit of CPX-351 over 7 ... CPX-351 improved survival without pronounced myelotoxicity in patients with AML-MR mutations, had no benefit over 7+3 in those with TP53 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39454204/

Long-term real-world evidence of CPX-351 of high-risk ... Long-term real-world evidence of CPX-351 of high-risk patients with AML identified high rate of negative MRD and prolonged OS · Authors.

7. nature.com nature.com/articles/s41408-025-01346-1

Newly diagnosed acute myeloid leukemia in unfit patients Response rates (CR/CRi:40-90%) and overall survival outcomes (3-year: 0–67%) following Ven-HMA therapy are highly variable and depend primarily ...

8. studyfinder.umn.edu studyfinder.umn.edu/studies/32260

UMN - StudyFinder The study will give these participants an investigational drug called bortezomib in combination with an approved drug for AML, CPX-351 (brand name: Vyxeos). The ...