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

NCT ID: NCT04155580

Last Updated: 2024-08-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-12
• Study Completion Date: 2022-01-14

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.

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

ASTX660

Intervention Type: DRUG

Capsule for oral administration

ASTX727

Intervention Type: DRUG

Tablet for oral administration

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)

Group Type: EXPERIMENTAL

ASTX660

Intervention Type: DRUG

Capsule for oral administration

ASTX727

Intervention Type: DRUG

Tablet for oral administration

Part 3

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

Group Type: EXPERIMENTAL

ASTX660

Intervention Type: DRUG

Capsule for oral administration

ASTX727

Intervention Type: DRUG

Tablet for oral administration

Interventions

ASTX660

Capsule for oral administration

Intervention Type: DRUG

ASTX727

Tablet for oral administration

Intervention Type: DRUG

Other Intervention Names

cedazuridine + decitabine

Eligibility Criteria

Inclusion Criteria

1. Have a projected life expectancy of at least 12 weeks, as assessed by the Investigator.

2. Have histological confirmation of AML by World Health Organization (WHO) 2016 criteria and are either:

1. refractory to intensive induction chemotherapy OR

2. relapsed after intensive induction chemotherapy or stem cell transplant OR

3. relapsed after or refractory to treatment with molecularly targeted and/or low-intensity chemotherapeutic regimens.

3. Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.

4. Have adequate renal function as demonstrated by measured or calculated creatinine clearance ≥60 mL/min.

5. Have adequate liver function as demonstrated by:

1. Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN)

2. Alanine aminotransferase (ALT) ≤2.5 × ULN

3. Bilirubin ≤1.5 × ULN - unless considered due to leukemic organ involvement.

6. 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

1. Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.

2. Known clinically active central nervous system (CNS) leukemia.

3. BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).

4. Diagnosis of acute promyelocytic leukemia (M3 AML or APML).

5. Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.

6. 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.

7. Presence of persistent toxicities of Grade >1 from prior treatment including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, and surgery (except for alopecia).

8. Hypersensitivity to decitabine, ASTX727, ASTX660, or any of their excipients.

9. Liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.

10. 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.

11. History of, or at risk for, cardiac disease.

12. 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).

13. 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.

14. 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.

15. 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).

16. 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California San Francisco

San Francisco, California, United States

Smilow Cancer Hospital

New Haven, Connecticut, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Northside Hospital - The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

Franciscan Health Indianapolis (Blood and Marrow Transplantation)

Indianapolis, Indiana, United States

The University of Kansas Clinical Research Center

Fairway, Kansas, United States

Mayo Clinic

Rochester, Minnesota, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

New York University Langone Health

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

ASTX660-02

Identifier Type: -

Identifier Source: org_study_id