Venetoclax and ASTX727 for the Treatment of Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia

NCT04746235 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2020-1007NCI-2021-00112
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the possible benefits of venetoclax and ASTX727 in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or elderly patients with newly diagnosed acute myeloid leukemia who are not candidates for intensive chemotherapy. Venetoclax may help block the formation of growths that may become cancer. ASTX727 is the combination of a fixed dose of 2 drugs, cedazuridine and decitabine. Cedazuridine may slow down how fast decitabine is broken down by the body, and decitabine may block abnormal cells or cancer cells from growing. Giving venetoclax and ASTX727 may help to control the disease.

Conditions

Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Overall response rate (ORR)

  Will be defined as the proportion of patients who had CR (complete remission), CRp (complete remission with incomplete platelet recovery), CRi (complete remission with incomplete count recovery), PR (partial response) or marrow clearance of blasts within 3 months of treatment initiation among adult patients with acute myeloid leukemia (AML). Response criteria will be modified from the International Working Group for AML. Will estimate the ORR for the combination treatments for each cohort, along with the 90% credible intervals. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

  Within 3 months of treatment initiation

• Overall incidence and severity of all adverse events

  Will be assessed by Common Toxicity Criteria version 5.0.

  Up to 5 years post treatment

Secondary Outcomes (2)

• Disease free survival

  Up to 5 years post treatment

• Overall survival

  Up to 5 years post treatment

Study Arms (1)

Treatment (decitabine and cedazuridine, venetoclax)

EXPERIMENTAL

Patients receive decitabine and cedazuridine PO daily on days 1-5 and venetoclax PO daily on days 1-28 of the first cycle and on days 1-21 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Decitabine and Cedazuridine; Drug: Venetoclax

Interventions

Decitabine and Cedazuridine DRUG

Given PO

Also known as: ASTX727, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, Inqovi

Treatment (decitabine and cedazuridine, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (decitabine and cedazuridine, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with AML by the World Health Organization (WHO) classification who have failed prior therapy, refractory to it or relapsed after prior response. Patients with isolated extramedullary AML are eligible (cohort 1)
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Confirmed newly diagnosed AML
• Ineligible for induction therapy defined as
• Either age \>= 75 years
• Or 18-74 years of age with at least one comorbidity (chronic heart failure \[CHF\] requiring therapy or eject fraction \[EF\] =\< 50%, carbon monoxide diffusing capability \[DLCO\] =\< 65% or forced expiratory volume in 1 second \[FEV1\] =\< 65%, or ECOG 2 or 3)
• Creatinine clearance ≥30 mL/min to \<45 mL/min
• Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0 × upper limit of normal (ULN)
• Creatinine clearance ≥ 45 ml/min unless related to the disease (e.g. infiltration)
• Total bilirubin \< 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
• Alanine aminotransferase (ALT) \< 3 x ULN unless considered due to leukemic involvement (by biopsy or imaging)
• Able to give written informed consent
• Oral hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and hydroxyurea while the patient is on active study treatment through cycle 1, as needed, for clinical benefit and after discussion with the principal investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
• Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment

You may not qualify if:

• Acute promyelocytic leukemia
• Prior therapy with a BCL2 inhibitor
• Symptomatic or uncontrolled CNS leukemia
• Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
• Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
• Pregnant or breastfeeding

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Bazinet A, Garcia-Manero G, Short N, Alvarado Y, Bataller A, Abuasab T, Islam R, Montalbano K, Issa G, Maiti A, Yilmaz M, Jain N, Masarova L, Kornblau S, Jabbour E, Montalban-Bravo G, Rausch CR, Pierce S, DiNardo CD, Kadia T, Daver N, Konopleva M, Huang X, Kantarjian H, Ravandi F. Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia: a phase 2 study. Lancet Haematol. 2024 Apr;11(4):e276-e286. doi: 10.1016/S2352-3026(24)00033-4. Epub 2024 Mar 4.

  PMID: 38452788 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

decitabine and cedazuridine drug combination; venetoclax

Condition Hierarchy (Ancestors)

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

Study Officials

• Farhad Ravandi-Kashani, MD

  M.D. Anderson Cancer Center

  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: February 1, 2021
• First Posted: February 9, 2021
• Study Start: February 22, 2021
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)