Description:
This phase II trial studies the effects of venetoxlax in combination with decitabine and
cedazuridine in treating patients with acute myeloid leukemia that has come back (relapsed)
or does not respond to treatment (refractory). Chemotherapy drugs, such as venetoclax and
decitabine, 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. Cedazuridine may
stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving
venetoxlax in combination with decitabine and cedazuridine may help to control acute myeloid
leukemia.
Title
- Brief Title: Venetoclax in Combination With Decitabine and Cedazuridine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
- Official Title: A Phase II Study of Venetoclax in Combination With 10-day Oral Decitabine in Relapsed/Refractory Acute Myeloid Leukemia
Clinical Trial IDs
- ORG STUDY ID:
2021-0248
- SECONDARY ID:
NCI-2021-05744
- SECONDARY ID:
2021-0248
- NCT ID:
NCT04975919
Conditions
- Recurrent Acute Biphenotypic Leukemia
- Recurrent Acute Myeloid Leukemia
- Refractory Acute Biphenotypic Leukemia
- Refractory Acute Myeloid Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Decitabine and Cedazuridine | ASTX727, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, Inqovi | Treatment (decitabine and cedazuridine, venetoclax) |
Venetoclax | ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto | Treatment (decitabine and cedazuridine, venetoclax) |
Purpose
This phase II trial studies the effects of venetoxlax in combination with decitabine and
cedazuridine in treating patients with acute myeloid leukemia that has come back (relapsed)
or does not respond to treatment (refractory). Chemotherapy drugs, such as venetoclax and
decitabine, 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. Cedazuridine may
stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving
venetoxlax in combination with decitabine and cedazuridine may help to control acute myeloid
leukemia.
Detailed Description
PRIMARY OBJECTIVE:
I. To determine the overall response rate (complete remission [CR], complete remission with
incomplete count recovery [CRi], MLFS and partial response [PR]) of 10-days decitabine and
cedazuridine (oral decitabine) and venetoclax in patients with refractory/relapsed acute
myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. To determine the duration of response, event-free survival (EFS), and overall survival
(OS) of patients with refractory/relapsed AML treated with this combination.
II. To determine the number of patients who achieve a hematologic improvement (HI) in
platelets, hemoglobin, or ANC and the number of patients who achieve > 50% reduction in
blasts on therapy with venetoclax/10-day oral decitabine.
III. To determine the safety of venetoclax in combination with 10-day oral decitabine in
patients with refractory/ relapsed AML.
IV. To determine the number of patients who transition towards stem cell transplantation upon
achieving response with the combination venetoclax/10-day oral decitabine regimen.
V. To determine the incidence of infectious complications per cycle with venetoclax in
combination with 10-day oral decitabine.
EXPLORATORY OBJECTIVE:
I. To investigate global gene expression profiles, cytometry by time of flight (CyTOF), BH3
profiling and other potential prognostic markers to explore predictors of antitumor activity
and/or resistance to treatment.
OUTLINE:
Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-10.
Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and
cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle
1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (decitabine and cedazuridine, venetoclax) | Experimental | Patients receive decitabine and cedazuridine PO QD on days 1-10. Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | - Decitabine and Cedazuridine
- Venetoclax
|
Eligibility Criteria
Inclusion Criteria:
- Patients with a diagnosis of relapsed or refractory AML (or biphenotypic or bilineage
leukemia including a myeloid component). Patients with isolated extramedullary AML are
eligible
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Creatinine < 2 unless related to the disease
- Direct bilirubin < 2 x upper limit of normal (ULN) unless increase is due to Gilbert's
disease or leukemic involvement
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULN
unless considered due to leukemic involvement
- In the absence of rapidly proliferative disease, the interval from prior treatment to
time of initiation will be at least 7 days for cytotoxic or non-cytotoxic
(immunotherapy) agents. Oral hydroxyurea and/or cytarabine (up to 2 g/m^2) for
patients with rapidly proliferative disease is allowed before the start of study
therapy, 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
- Male subjects must agree to refrain from unprotected sex and sperm donation from
initial study drug administration until 90 days after the last dose of study drug
- Willing and able to provide informed consent
Exclusion Criteria:
- Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia
(French-American-British [FAB] class M3-AML)
- Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant
(patients without active GVHD on chronic suppressive immunosuppression and/or
phototherapy for chronic skin GVHD are permitted after discussion with the PI)
- Patients with any severe gastrointestinal or metabolic condition which could interfere
with the absorption of oral study medications as determined by the investigator
- Patients with symptomatic CNS leukemia or patients with poorly controlled 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 active hepatitis B (HBV) or hepatitis C (HCV) infection or known human
immunodeficiency virus (HIV) infection
- Subject has a white blood cell count > 10 x 10^9/L. (Note: Hydroxyurea is permitted to
meet this criterion)
- 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
- Nursing women, women of childbearing potential (WOCBP) with positive urine or serum
pregnancy test, or women of childbearing potential who are not willing to maintain
adequate contraception
- Appropriate highly effective method(s) of contraception include oral or
injectable hormonal birth control, intrauterine device (IUD), and double barrier
methods (for example a condom in combination with a spermicide)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall response rate (ORR) |
Time Frame: | Within 4 cycles of treatment (each cycle is 28 days) |
Safety Issue: | |
Description: | Defined as the proportion of patients who had complete remission (CR), complete remission with incomplete count recovery (CRi), partial response (PR) or MLFS. Will estimate the ORR for the combination treatment, along with the Bayesian 95% credible interval. |
Secondary Outcome Measures
Measure: | Proportion of achieving HI |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Will estimate for the combination treatment, along with the Bayesian 95% credible interval. |
Measure: | Number of patients who transition towards stem cell transplantation |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Will estimate for the combination treatment, along with the Bayesian 95% credible interval. |
Measure: | Incidence of infectious complications |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Will estimate for the combination treatment, along with the Bayesian 95% credible interval. |
Measure: | Event-free survival (EFS) |
Time Frame: | Time interval between treatment start until disease progression, relapse/refractory, or death due to any cause, assessed up to 2 years |
Safety Issue: | |
Description: | The Kaplan-Meier method will be used to estimate the survival probabilities of time-to-event variables such as EFS. Log-rank tests will be used to compare among subgroups of patients in terms of the time-to-event variables. |
Measure: | Overall survival (OS) |
Time Frame: | Time interval between treatment start until death due to any cause, assessed up to 2 years |
Safety Issue: | |
Description: | The Kaplan-Meier method will be used to estimate the survival probabilities of time-to-event variables such as OS. Log-rank tests will be used to compare among subgroups of patients in terms of the time-to-event variables. |
Measure: | Duration of response |
Time Frame: | Time from response till progression, relapse/refractory, or death, assessed up to 2 years |
Safety Issue: | |
Description: | |
Measure: | Gene expression profiles |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Will examine the association between gene expression profiles and prognostic markers and overall response and/or resistance will be assessed through logistic regression analyses. Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
July 26, 2021