Clinical Trials /

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

NCT04155580

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ASTX660-02
  • NCT ID: NCT04155580

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
ASTX660Part 1
ASTX727cedazuridine + decitabinePart 1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1ExperimentalASTX660 once daily (Days 1-7 and 15-21 per 28-day cycle) + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
  • ASTX660
  • ASTX727
Part 2ExperimentalASTX660 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)
  • ASTX660
  • ASTX727
Part 3ExperimentalASTX660 at the recommended dose for expansion identified in Part 2 + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
  • ASTX660
  • ASTX727

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.

         15. Prior treatment with hypomethylating agent (ie, decitabine or azacitidine) for more
             than 2 cycles.

         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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety Assessment: Number of participants with treatment-emergent adverse events (TEAEs)
Time Frame:Up to 30 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Time to response: Time from first dose to the first documented evidence of response
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Duration of response: Time from the start of response until disease progression or relapse
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Overall survival: Time since first dose until death due to any cause
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Composite complete response: Number of participants (sum of CR+CRi)
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Complete response with partial hematological recovery (CRh): Number of participants
Time Frame:Up to Month 30
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Astex Pharmaceuticals, Inc.

Trial 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

Last Updated

November 6, 2019