- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04746235
Venetoclax and ASTX727 for the Treatment of Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia
A Phase 2 Study of Venetoclax in Combination With ASTX727 in Patients With Relapsed/Refractory Acute Myeloid Leukemia, and Newly Diagnosed Elderly Patients With AML Who Are Not Candidates for Intensive Chemotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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 ((≥ 75 years or ≥ 18 years with comorbidities) 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
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Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Principal Investigator:
- Farhad Ravandi-Kashani
-
Contact:
- Farhad Ravandi-Kashani
- Phone Number: 713-745-0394
- Email: fravandi@mdanderson.org
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 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
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (decitabine and cedazuridine, venetoclax)
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.
|
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR)
Time Frame: Within 3 months of treatment initiation
|
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
Time Frame: Up to 5 years post treatment
|
Will be assessed by Common Toxicity Criteria version 5.0.
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Up to 5 years post treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease free survival
Time Frame: Up to 5 years post treatment
|
Will be estimated using the method of Kaplan and Meier.
Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
|
Up to 5 years post treatment
|
Overall survival
Time Frame: Up to 5 years post treatment
|
Will be estimated using the method of Kaplan and Meier.
Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
|
Up to 5 years post treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Farhad Ravandi-Kashani, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Hematologic Diseases
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine
- Venetoclax
- Decitabine and cedazuridine drug combination
Other Study ID Numbers
- 2020-1007 (Other Identifier: M D Anderson Cancer Center)
- NCI-2021-00112 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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