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

  • STATUS
    Recruiting
  • End date
    Oct 15, 2022
  • participants needed
    40
  • sponsor
    M.D. Anderson Cancer Center
Updated on 15 March 2021

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.

Description

PRIMARY OBJECTIVES:

I. To determine the overall response rate (ORR) of decitabine and cedazuridine (ASTX727) in combination with venetoclax in patients with refractory/relapsed acute myeloid leukemia (AML).

II. To determine the overall response rate (ORR) of ASTX727 in combination with venetoclax in elderly (> 60 year old) patients with newly diagnosed acute myeloid leukemia (AML) not eligible for intensive chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.

II. To determine similar outcomes for newly diagnosed patients with AML who are not candidates for intensive chemotherapy.

III. To determine the safety of venetoclax in combination with ASTX727 in patients with refractory/ relapsed AML, and newly diagnosed patients with AML not candidates for intensive chemotherapy.

IV. To determine the number of relapsed patients able to proceed to stem cell transplantation upon achieving response with the combination venetoclax/ASTX727 regimen.

EXPLORATORY OBJECTIVE:

I. To characterize the pharmacokinetic (PK) profiles of ASTX727 when combined with venetoclax.

OUTLINE

Patients receive decitabine and cedazuridine orally (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.

After completion of study treatment, patients with an objective response are followed every 3-6 months for up to 5 years.

Details
Condition Acute myeloid leukemia, Acute Myelogenous Leukemia (AML), Refractory Acute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia, acute myelogenous leukemia, anll, acute myeloblastic leukemia, refractory acute myeloid leukemia (aml)
Treatment venetoclax, Decitabine and Cedazuridine
Clinical Study IdentifierNCT04746235
SponsorM.D. Anderson Cancer Center
Last Modified on15 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
For cohort 2 (frontline elderly or unfit AML AML), the following inclusion criteria
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 < 2 x upper limit of normal 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 and/or one dose of cytarabine (up to 2 g/m^2) 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
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

Exclusion Criteria

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
Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
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
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