Venetoclax and Azacitidine for Non-Elderly Adult Patients With Acute Myeloid Leukemia

NCT03573024 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 18-0709.ccNCI-2018-02119
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to treat non-elderly adult patients, who were previously untreated for acute myeloid leukemia, using venetoclax and azacitidine.

Conditions

Acute Myeloid Leukemia

Keywords

Venetoclax; Azacitidine; Non-Elderly; Previously Untreated

Outcome Measures

Primary Outcomes (1)

• Response Rate, measured by the European Leukemia Net definition: (CRMRD-+CR+CRi+MLFS)

  The (CRMRD-+CR+CRi+MLFS) shows non-inferiority of venetoclax with azacitidine when compared with historical controls who received induction chemotherapy.

  Study start date to study end date, or death, whichever comes first, up to 4 years

Secondary Outcomes (5)

• Incidence of Minimal Residual Disease (MRD) Negative Responses

  Study start date to study end date, or death, whichever comes first, up to 4 years

• Remission Duration

  Study start date to study end date, or death, whichever comes first, up to 4 years

• One Year Event Free Survival

  Study start date to study end date, or death, whichever comes first, up to 4 years

• Overall Survival

  Study start date to study end date, or death, whichever comes first, up to 4 years

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Study start date to study end date, or death, whichever comes first, up to 4 years

Study Arms (1)

Azacitidine and Venetoclax

EXPERIMENTAL

Azacitidine will be given intravenously for 7 days. Venetoclax will be given orally. The patient will start out with 100mg and progress to 600mg. Once 600mg is reached, the patient will stay at this dose until the 28 day cycle is finished.

Drug: Azacitidine; Drug: Venetoclax

Interventions

Azacitidine DRUG

On day 1 of cycle 1, azacitidine 75 mg/m2 SC or IV will be given, and will continue for 7 days.

Azacitidine and Venetoclax

Venetoclax DRUG

Starting on day 1 of cycle 1, venetoclax will be initiated. It will be dose escalated to a target dose of 600 mg in the following manner: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3 and 600 mg on day 4. The patient then continues to take the 600mg dose for the remainder of the 28 day cycle. Each dose of venetoclax will be self-administered with approximately 240 mL of water within 30 minutes after the completion of a meal, preferably breakfast. The dose should be administered at the same time each day. On days the subject is given azacitidine, venetoclax must be given first.

Azacitidine and Venetoclax

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A subject will be eligible for study participation if he/she meets the following criteria within 28 days prior to the first day of therapy (bone marrow biopsy can be performed 28 days prior to the first day of therapy). Historical records are permitted per Investigator discretion.
• Subject must have confirmation of non-APL and AML by WHO criteria45
• Subject must have received no prior treatment for AML
• Age ≥18 years, ≤59 years
• Without clinical signs of active central nervous system disease
• Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2
• Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
• Subject must have adequate liver function as demonstrated by:
• aspartate aminotransferase (AST) ≤ 3.0 × ULN\*
• alanine aminotransferase (ALT) ≤ 3.0 × ULN\*
• bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome\* \* Unless considered due to leukemic organ involvement
• Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.
• Female subjects who are pre-menopausal and have not had a hysterectomy or oophorectomy must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting therapy; 2) throughout the entire duration of treatment; 3) during dose interruptions; and 4) for at least 90 days after discontinuation of therapy (last dose of study drug).
• Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed screening procedures.

You may not qualify if:

• A subject will not be eligible for study participation if he/she meets any of the following criteria:
• Subject is known to be positive for HIV. HIV testing is not required.
• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, anti-HBs+ and anti-HBc-) may participate
• Subject has received within 7 days prior to the first dose of study drug:steroid therapy for anti-neoplastic intent; strong and moderate CYP3A inhibitors; strong and moderate CYP3A inducers.
• Subject is informed that consumption of the following fruits is prohibited 3 days prior to the initiation of study treatment and throughout participation: grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit.
• Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
• New York Heart Association heart failure \> class 2
• Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia
• Subject has a malabsorption syndrome or other condition that precludes enteral route of administration
• Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal)
• Subject has a history of other malignancies prior to study entry, with the exception of:
• Adequately treated in situ carcinoma of the breast or cervix uteri
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
• Prostate cancer with no plans for therapy of any kind
• Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• AbbVie: collaborator

Study Sites (1)

Universtiy of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Daniel Pollyea, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: June 28, 2018
• Study Start: November 28, 2018
• Primary Completion: April 14, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 7, 2025

Record last verified: 2025-05

Locations

US (1)