Recruiting

Phase 2

Azacitidine & VenetoclaxAzacitidine or Decitabine With Venetoclax for Acute Myeloid Leukemia With Prior Hypomethylating Agent Failure

Sponsor:

Brian Jonas

Code:

NCT04905810

Conditions

Acute Myeloid Leukemia

Recurrent Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Azacitidine

Decitabine

Venetoclax

Study Details

Brief summary:

This phase II trial evaluates the effect of azacitidine or decitabine and venetoclax in treating patients with acute myeloid leukemia that has not been treated before (treatment naive) or has come back (relapsed). Chemotherapy drugs, such as azacitidine, decitabine, and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Acute Myeloid Leukemia

Recurrent Acute Myeloid Leukemia

Study ID

NCT04905810

Start date

Feb 9, 2022

Status verified date

May, 2024

Completion date

Dec 1, 2025

Anticipated

Primary completion date

May 1, 2025

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Ability to understand and the willingness to sign a written informed consent
Diagnosis of AML by World Health Organization (WHO) 2016 criteria (Arber 2016)
Age >= 18 years
Treatment naïve and eligible for venetoclax plus HMA: \* Age >= 75 OR \* Age >= 18-74 with at least one of the following co-morbidities: \*\* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 \*\* Cardiac history of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) =< 50% or chronic unstable angina \*\* Carbon monoxide diffusing capability (DLCO) =< 65% or forced expiratory volume in 1 second (FEV1) =< 65% \*\* Creatinine clearance >= 30 mL/min to =< 45 mL/min \*\* Moderate hepatic impairment with total bilirubin > 1.5 to =< 3 x upper limit of normal (ULN) \*\* Any other situation that the investigator judges to be incompatible with intensive chemotherapy must be reviewed with the study chair before study enrollment
Patient experienced HMA failure for an antecedent hematologic disorder (e.g. myelodysplastic syndrome) prior to study entry (Santini 2019), defined as: \* Disease progression or stable disease as best response to >= 4 cycles of HMA or >= 2 cycles of HMA combination therapy (primary resistance) OR \* Relapse or progression after prior response to HMA (secondary resistance)
Prior decitabine and/or azacitidine, including oral formulations, for antecedent hematologic disorder is required. The patient should be treatment naïve for the AML diagnosis
Prior allogeneic hematopoietic transplant for antecedent hematologic disorder is allowed if done at least 3 months prior to enrollment and there is no evidence of active graft versus host disease (GVHD) or requirement for systemic immune suppression
ECOG performance status of: \* 0 to 2 for subjects >= 75 years of age OR \* 0 to 3 for subjects >= 18-74 years of age
Whole blood cell (WBC) >= 25,000/mm\^3 at the start of study therapy (leukapheresis and hydroxyurea areallowed to meet this criteria)
Total bilirubin =, 1.5 x institution's ULN unless related to AML or Gilbert's syndrome (subjects who are >= 18-74 may have a total bilirubin of =< 3 x institution's ULN)
Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SPGT) =< 3 x institutional ULN unless related to AML
Creatinine clearance >= 30 mL/min (calculated by the Cockcroft Gault formula or measured by 24-hours urine collection)
Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. \* A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: \*\* Has not undergone a hysterectomy or bilateral oophorectomy; or \*\* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing
Able to swallow and retain oral medication

Exclusion Criteria:

Current or anticipated use of other investigational agents within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration
Diagnosis of acute promyelocytic leukemia
Active central nervous system involvement by AML
Anticancer therapies, including investigational therapy, chemotherapy, targeted small molecule agents, or radiotherapy within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration. Biologic agents (e.g. monoclonal antibodies) given for anti-neoplastic intent within 30 days prior to the first dose and throughout venetoclax administration
Prior therapy with venetoclax
Known diagnosis of human immunodeficiency virus (HIV) infection or known active hepatitis A, B or C infection with the exception of those with an undetectable viral load and CD4+ T-cell (CD4+) counts >= 350 cells/μL within 3 months of starting study treatment. Should have no titers within 28d of day 1. Patients with hepatitis C virus (HCV) infection should have completed curative antiviral treatment
Known strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment
Subject has consumed grapefruit, grapefruit products, Seville oranges or starfruit within 3 days prior to the initiation of study treatment
Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements)
History of other malignancies, except for malignancy treated with curative intent with no known active disease present for >= 1 year; treated non-melanoma skin cancer; and localized, cured prostate and cervical cancer
Evidence of uncontrolled active systemic infection requiring therapy (viral, bacterial, or fungal). Fever of unknown origin is not an exclusion criterion, as this may be disease related
History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
Subject has a malabsorption syndrome of other condition that precludes enteral route of administration
Subjects with a cardiovascular disability status of New York Heart Association class greater than 2
Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (azacitidine, decitabine, venetoclax)

Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7 (for patients with prior decitabine use), or decitabine IV on days 1-5 (for patients with prior azacitidine), and venetoclax PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Azacitidine

Given IV

Decitabine

Given IV

Venetoclax

Given PO

Primary outcome measure

Overall response rate [ Time Frame: Up to 1 year ]

Central Contacts and Locations

Locations

UCSF-Fresno

Recruiting

Clovis, California, United States, 93611

Contacts

Mohammed Bukari, MD

559-387-1900 mohammed.bukari@ucsf.edu

Principal Investigator:

Mohammed Bukari, MD

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Brian A. Jonas

916-734-3771 bajonas@ucdavis.edu

Principal Investigator:

Brian A. Jonas

More Information

Sponsor

Brian Jonas

Last update posted

May 29, 2024

Last verified

May, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brian Jonas on 2024-05-29.