Pevonedistat + Venetoclax + Azacitidine for Acute Myeloid Leukemia

(PEVENAZA Trial)

Recruiting at 66 trial locations

Overseen By Takeda Study Registration Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Must not be taking: Hypomethylating agents

Disqualifiers: BCR-ABL1 translocation, CNS involvement, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

164 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination for adults with AML who can't handle intensive chemotherapy. The drugs work together to stop cancer cells from growing and help kill them. Venetoclax combined with azacitidine has become a new standard of care for patients unfit for intensive chemotherapy.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

Adults recently diagnosed with Acute Myeloid Leukemia (AML) who can't undergo intensive chemotherapy due to age or health issues like poor performance status, heart or lung problems, reduced kidney function, or liver disorders. Participants should not have had certain prior treatments for AML, no genetic acute promyelocytic leukemia, and must be unfit for stem cell transplantation.

Inclusion Criteria

Has clinical laboratory values within specified parameters.

I cannot receive standard chemotherapy due to my age or other health issues.

I have been diagnosed with AML according to WHO criteria.

Exclusion Criteria

My AML has affected or has a history of affecting my brain or spinal cord.

I have a history of blood cancer with a specific genetic change.

Has a WBC count ≥25 × 10^9/L

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Pevonedistat + Venetoclax + Azacitidine or Venetoclax + Azacitidine in 28-day cycles

Up to 36 months

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue treatment as long as they are benefiting from it

Long-term

Treatment Details

Interventions

• Azacitidine
• Pevonedistat
• Venetoclax

Trial Overview The trial is testing if adding Pevonedistat to the combination of Venetoclax and Azacitidine improves outcomes in AML patients compared to just Venetoclax and Azacitidine. Patients will receive these drugs in cycles lasting 28 days each and may continue treatment as long as it's beneficial.

Participant Groups

Group I: Pevonedistat 20 mg/m^2 + Venetoclax 100/200/400 mg + Azacitidine 75 mg/m^2 Experimental Treatment 3 Interventions

Pevonedistat 20 mg/m\^2 as a 60-minute IV infusion on Days 1, 3, and 5 in each 28-day cycle plus venetoclax 100 mg tablet orally on Day 1; 200 mg on Day 2; thereafter, at 400 mg on Day 3 through Day 28 in Cycle 1 (cycle length= 28 days) and 400 mg on Days 1 through 28 in Cycle 2 and beyond if tolerated. Following the confirmation of remission in Cycle 1 or thereafter, venetoclax 400 mg was administered on Day 1 through 21 or 28 as per Investigator's discretion, plus azacitidine 75 mg/m\^2 IV or SC dosing on Day 1 through 7 or Days 1 through 5, Days 8, and 9 in each cycle up to primary completion date: 06 September 2022.

Group II: Venetoclax 100/200/400 mg + Azacitidine 75 mg/m^2 Active Control 2 Interventions

Venetoclax 100 mg tablet orally on Day 1; 200 mg on Day 2; thereafter, at 400 mg on Day 3 through Day 28 in Cycle 1 (cycle length= 28 days) and 400 mg on Days 1 through 28 in Cycle 2 and beyond if tolerated. Following the confirmation of remission in Cycle 1 or thereafter, venetoclax 400 mg was administered on Day 1 through 21 or 28 as per Investigator's discretion, plus azacitidine 75 mg/m\^2 intravenous (IV) or subcutaneous (SC) dosing on Days 1 through 7 or Days 1 through 5, Days 8, and 9 in each cycle up to primary completion date: 06 September 2022.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier