Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion

Description

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.

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)

Details

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.

Keywords

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

Eligibility

You can join if…

Open to people ages 18 years and up

  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:
  3. refractory to intensive induction chemotherapy OR
  4. relapsed after intensive induction chemotherapy or stem cell transplant OR
  5. relapsed after or refractory to treatment with molecularly targeted and/or low-intensity chemotherapeutic regimens.
  6. Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
  7. Have adequate renal function as demonstrated by measured or calculated creatinine clearance ≥60 mL/min.
  8. Have adequate liver function as demonstrated by:
  9. Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN)
  10. Alanine aminotransferase (ALT) ≤2.5 × ULN
  11. Bilirubin ≤1.5 × ULN - unless considered due to leukemic organ involvement.
  12. 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 CAN'T join if...

  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).

Locations

  • University of California San Francisco accepting new patients
    San Francisco California 94143 United States
  • The University of Texas MD Anderson Cancer Center accepting new patients
    Houston Texas 77030 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Astex Pharmaceuticals, Inc.
ID
NCT04155580
Phase
Phase 1
Study Type
Interventional
Last Updated