- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04155580
A Study of ASTX660 as a Single Agent and in Combination With ASTX727 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)
A Phase 1, Parallel, Open-Label Study of the Safety and Tolerability, Pharmacokinetics, and Antileukemic Activity of ASTX660 as a Single Agent and in Combination With ASTX727 in Subjects With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a three-part dose escalation and dose expansion Phase 1 study of ASTX660 alone and in combination with ASTX727 in adults with R/R AML.
Part 1 is an open-label, single arm, dose escalation with ASTX660 in combination with ASTX727 at the standard fixed dose combination (FDC).
Part 2 is an open-label, randomized, dose escalation intended to evaluate ASTX660 as a monotherapy and ASTX660 in combination with ASTX727 FDC.
Part 3 is an exploratory single arm dose expansion to further expand the number of participants treated with ASTX660 in combination with ASTX727 FDC.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
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San Francisco, California, United States, 94143
- University of California San Francisco
-
-
Connecticut
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New Haven, Connecticut, United States, 06510
- Smilow Cancer Hospital
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-
Florida
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Miami, Florida, United States, 33136
- Sylvester Comprehensive Cancer Center
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Georgia
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Atlanta, Georgia, United States, 30342
- Northside Hospital - The Blood and Marrow Transplant Group of Georgia
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Illinois
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Chicago, Illinois, United States, 60637
- The University of Chicago Medical Center
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Indiana
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Indianapolis, Indiana, United States, 46237
- Franciscan Health Indianapolis (Blood and Marrow Transplantation)
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Kansas
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Fairway, Kansas, United States, 66205
- The University of Kansas Clinical Research Center
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Comprehensive Cancer Center
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New York, New York, United States, 10029
- Mount Sinai Medical Center
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New York, New York, United States, 10016
- New York University Langone Health
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- Lineberger Comprehensive Cancer Center
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt - Ingram Cancer Center
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Texas
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Houston, Texas, United States, 77030
- The University of Texas MD Anderson Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Have a projected life expectancy of at least 12 weeks, as assessed by the Investigator.
Have histological confirmation of AML by World Health Organization (WHO) 2016 criteria and are either:
- refractory to intensive induction chemotherapy OR
- relapsed after intensive induction chemotherapy or stem cell transplant OR
- relapsed after or refractory to treatment with molecularly targeted and/or low-intensity chemotherapeutic regimens.
- Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
- Have adequate renal function as demonstrated by measured or calculated creatinine clearance ≥60 mL/min.
Have adequate liver function as demonstrated by:
- Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN)
- Alanine aminotransferase (ALT) ≤2.5 × ULN
- Bilirubin ≤1.5 × ULN - unless considered due to leukemic organ involvement.
- Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
Exclusion Criteria:
- Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
- Known clinically active central nervous system (CNS) leukemia.
- BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Diagnosis of acute promyelocytic leukemia (M3 AML or APML).
- Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
- Graft Versus Host Disease (GVHD), or any GVHD requiring treatment with immunosuppression. Any GVHD treatment (including calcineurin inhibitors) must be discontinued at least 28 days prior to Day 1 of study treatment.
- Presence of persistent toxicities of Grade >1 from prior treatment including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, and surgery (except for alopecia).
- Hypersensitivity to decitabine, ASTX727, ASTX660, or any of their excipients.
- Liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
- Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise participant safety, or the integrity of study outcomes, or interfere with the absorption or metabolism of ASTX660 or ASTX727.
- History of, or at risk for, cardiac disease.
- Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV), or active hepatitis C virus (HCV) infection (participants with laboratory evidence of no active replication will be permitted).
- Known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the participant to high risk of noncompliance with the protocol treatment or assessments.
- Treated with any investigational therapy within 2 weeks of the first dose of study treatment or treatment with a myelosuppressive therapy within 4 weeks of the first dose of study treatment.
- In Parts 1 and 2, prior treatment with decitabine for more than 2 cycles. In Part 3, any treatment with an HMA (azacitidine or decitabine, for more than one cycle).
- Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to ASTX660-02 (Note: G-tube administration is not allowed).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1
ASTX660 once daily (Days 1-7 and 15-21 per 28-day cycle) + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
|
Capsule for oral administration
Tablet for oral administration
Other Names:
|
Experimental: Part 2
ASTX660 once daily (Days 1-7 and 15-21 per 28-day cycle) as a single agent or in combination with ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
|
Capsule for oral administration
Tablet for oral administration
Other Names:
|
Experimental: Part 3
ASTX660 at the recommended dose for expansion identified in Part 2 + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
|
Capsule for oral administration
Tablet for oral administration
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety Assessment: Number of participants with treatment-emergent adverse events (TEAEs)
Time Frame: Up to 30 months
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Up to 30 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Response rate: Number of participants achieving complete response (CR), complete response with incomplete hematological recovery (CRi), and partial response (PR) as determined by the European LeukemiaNet (ELN) 2017 response criteria for AML
Time Frame: Up to 30 months
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Up to 30 months
|
Time to response: Time from first dose to the first documented evidence of response
Time Frame: Up to 30 months
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Up to 30 months
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Duration of response: Time from the start of response until disease progression or relapse
Time Frame: Up to 30 months
|
Up to 30 months
|
Overall survival: Time since first dose until death due to any cause
Time Frame: Up to 30 months
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Up to 30 months
|
Composite complete response: Number of participants (sum of CR+CRi)
Time Frame: Up to 30 months
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Up to 30 months
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Complete response with partial hematological recovery (CRh): Number of participants
Time Frame: Up to Month 30
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Up to Month 30
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Pharmacokinetic parameter: Area under the curve (AUC)
Time Frame: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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Pharmacokinetic parameter: Maximum plasma concentration (Cmax)
Time Frame: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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Pharmacokinetic parameter: Minimum plasma concentration (Cmin)
Time Frame: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax)
Time Frame: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
|
Pharmacokinetic parameter: Half-life (t½)
Time Frame: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
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On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ASTX660-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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