Pevonedistat, Azacitidine (or Decitabine), and Venetoclax for the Treatment of Patients With Acute Myelogenous Leukemia

Stopped early · Phase 1

Conditions studied: Acute Myelogenous Leukemia

In brief

This is a phase Ib study with a 3 + 3 dose escalation design followed by a dose-expansion phase.

Key facts

Study ID

NCT04172844

Run by

Medical College of Wisconsin

People needed

16

Starts

2020-01-13

Expected to finish

2022-02-27

Last updated by the study team

2024-06-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Male or female subjects 18 years or older.
• Patients must have a diagnosis of morphologically documented AML or secondary AML [from prior conditions, such as myelodysplastic syndrome (MDS), or therapy-related AML (t-AML), as defined by World Health Organization (WHO) criteria.
• During the dose-escalation phase, only subjects with relapsed/refractory AML will be eligible.
• During the expansion phase, subjects with relapsed/refractory AML will be eligible OR subjects with newly diagnosed AML unable or unwilling to receive intensive induction chemotherapy will be eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Clinical laboratory values within the following parameters:
• Albumin >2.7 g/dL.
• Total bilirubin ≤ institutional upper limit of normal (ULN). Patient with total bilirubin > ULN may enroll if direct bilirubin ≤1.5 x institutional ULN of the direct bilirubin.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × institutional ULN.
• Creatinine clearance ≥ 30 mL/min (calculated by Cockcroft-Gault formula).
• White blood cell (WBC) count < 25,000/μL before administration of pevonedistat on cycle 1 day 1. (Note: Hydroxyurea may be used to meet this criterion.)
• Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.5 institutional ULN.
• Female subjects who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential:
• Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through four months after the last dose of study drug (female and male condoms should not be used together), OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).
• Male subjects, even if surgically sterilized (i.e., status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through and through four months after the last dose of study drug (female and male condoms should not be used together), OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)

You may not qualify if…

• Acute promyelocytic leukemia.
• Extramedullary only relapse AML.
• Treatment with systemic antineoplastic therapy or radiation within 14 days before the study enrollment. The use of hydroxyurea for leukoreduction is permitted. Subjects must have recovered from the side effects of prior therapy per treating physician discretion.
• Hematopoietic Stem Cell Transplantation (HCT) within 100 days of enrollment, or evidence of veno-occlusive disease (VOD) at any time post-transplant, or active acute graft-versus-host disease requiring systemic immunosuppressive therapy.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
• Current systemic treatment with strong or moderate cytochrome P3A (CYP3A) inducers within seven days prior to enrollment.
• Any evidence of spontaneous tumor lysis syndrome (TLS).
• Active, significant, uncontrolled infection or severe infectious disease requiring therapy (bacterial, viral or fungal) as per the discretion of the treating physician.
• Presence of another active malignancy (requiring treatment) diagnosed within 12 months with the exception of
• adequately treated non-melanoma skin cancer.
• adequately treated melanoma grade 2 or less.
• cervical intraepithelial neoplasia.
• adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast.
• basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin.
• adequately treated prostate cancer.
• Life-threatening illness with life expectancy < 6 months unrelated to cancer.
• Known HIV positive patients who do not meet the following criteria:
• Cluster of differentiation (CD4) count > 350 cells/mm\^3.
• Undetectable viral load.
• Maintained on modern therapeutic regimens utilizing non-cytochrome (CYP)-interactive agents.
• No history of AIDS-defining opportunistic infections.
• Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection.
• Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
• Known hepatic cirrhosis or severe pre-existing hepatic impairment
• Known cardiopulmonary disease defined as:

Where it is running

• Mayo Clinic — Rochester, Minnesota, United States
• Froedtert Hospital and the Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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