A Study of ASTX660 as a Single Agent and in Combination With ASTX727 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)

NCT04155580 | Terminated Phase 1 FDA Drug

• 1 other identifier: ASTX660-02
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 15

Brief Summary

To evaluate the safety, pharmacokinetics (PK), and efficacy of ASTX660 when given alone and in combination with ASTX727 in participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). The duration of the study is expected to be approximately 30 months.

Conditions

Acute Myeloid Leukemia

Keywords

AML; Bone marrow; CMML; MDS; ASTX727; ASTX660; cIAP1; Cellular inhibitor of apoptosis protein; XIAP; CDAi; Cytidine deaminase inhibitor; Cedazuridine; Decitabine; Acute myeloid leukemia; Chronic myelomonocytic leukemia; Myelodysplastic syndrome

Outcome Measures

Primary Outcomes (1)

• Safety Assessment: Number of participants with treatment-emergent adverse events (TEAEs)

  Up to 30 months

Secondary Outcomes (11)

• 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

  Up to 30 months

• Time to response: Time from first dose to the first documented evidence of response

  Up to 30 months

• Duration of response: Time from the start of response until disease progression or relapse

  Up to 30 months

• Overall survival: Time since first dose until death due to any cause

  Up to 30 months

• Composite complete response: Number of participants (sum of CR+CRi)

  Up to 30 months

Study Arms (3)

Part 1

EXPERIMENTAL

ASTX660 once daily (Days 1-7 and 15-21 per 28-day cycle) + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)

Drug: ASTX660; Drug: ASTX727

Part 2

EXPERIMENTAL

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)

Drug: ASTX660; Drug: ASTX727

Part 3

EXPERIMENTAL

ASTX660 at the recommended dose for expansion identified in Part 2 + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)

Drug: ASTX660; Drug: ASTX727

Interventions

ASTX660 DRUG

Capsule for oral administration

Part 1; Part 2; Part 3

ASTX727 DRUG

Tablet for oral administration

Also known as: cedazuridine + decitabine

Part 1; Part 2; Part 3

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (15)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Smilow Cancer Hospital

New Haven, Connecticut, 06510, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Northside Hospital - The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Franciscan Health Indianapolis (Blood and Marrow Transplantation)

Indianapolis, Indiana, 46237, United States

Location

The University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

ASTX-660; decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 7, 2019
• Study Start: June 12, 2020
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: August 2, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)