Clinical Trials /

STAT Inhibitor OPB-111077 and Decitabine in Treating Patients With Acute Myeloid Leukemia That Is Refractory or Newly Diagnosed and Ineligible for Intensive Chemotherapy

NCT03063944

Description:

This phase I trial studies the side effects and best dose of STAT inhibitor OPB-111077 when given together with decitabine in treating patients with acute myeloid leukemia that does not respond to treatment or is newly diagnosed and ineligible for intensive chemotherapy. STAT inhibitor OPB-111077 and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: STAT Inhibitor OPB-111077 and Decitabine in Treating Patients With Acute Myeloid Leukemia That Is Refractory or Newly Diagnosed and Ineligible for Intensive Chemotherapy
  • Official Title: Phase I Trial of OPB-111077 in Combination With Decitabine for the Treatment of AML Refractory to or Ineligible for Intensive Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 16C.773
  • NCT ID: NCT03063944

Conditions

  • Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
STAT Inhibitor OPB-111077OPB-111077Treatment (STAT inhibitor OPB-111077, decitabine)
Decitabine127716, 2'-Deoxy-5-azacytidine, 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one, 2353-33-5, Dacogen, DeoxyazacytidineTreatment (STAT inhibitor OPB-111077, decitabine)

Purpose

This phase I trial studies the side effects and best dose of STAT inhibitor OPB-111077 when given together with decitabine in treating patients with acute myeloid leukemia that does not respond to treatment or is newly diagnosed and ineligible for intensive chemotherapy. STAT inhibitor OPB-111077 and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of STAT inhibitor OPB-111077 (OPB-111077) in
      combination with decitabine.

      SECONDARY OBJECTIVES:

      I. To describe any preliminary efficacy of OPB-111077 in combination with decitabine in
      patients with acute myeloid leukemia (AML).

      II. To measure adenosine triphosphate (ATP) generation and perform metabolomics in patients
      with AML who are receiving OPB-111077 and decitabine.

      III. To assess apoptosis and proliferation assays in patients with AML who are receiving
      OPB-111077 and decitabine.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (STAT inhibitor OPB-111077, decitabine)ExperimentalPatients receive STAT inhibitor OPB-111077 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive decitabine IV on days 8-12. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
  • STAT Inhibitor OPB-111077
  • Decitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologic evidence of high risk acute myeloid leukemia defined as
             one of the following:

               -  Primary refractory non-M3 AML

                  ** Evidence of leukemia after any therapy which, in the opinion of the
                  investigator, would be appropriate for therapy with OPB-111077 and decitabine

               -  Newly diagnosed non-M3 AML not eligible for intensive induction chemotherapy

          -  Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             2 or less

          -  Subjects must have a life expectancy of at least 4 weeks

          -  Subjects must be able to consume oral medication

          -  Subjects must have recovered from the toxic effects of any prior chemotherapy to <
             grade 1 (except alopecia)

          -  Creatinine =< 2.0mg/dL

          -  Total bilirubin =< 2 x upper limit of normal (ULN)

          -  Serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =< 2 x ULN

          -  Negative pregnancy test for women with child-bearing potential

          -  Patients must be able to sign consent and be willing and able to comply with scheduled
             visits, treatment plan and laboratory testing

        Exclusion Criteria:

          -  Subjects with FAB M3 (t(15;17)(q22;q21)[PML-RARalpha]) are not eligible

          -  Subjects must not be receiving any chemotherapy agents (except hydroxyurea);
             intrathecal methotrexate and cytarabine are permissible

          -  Subjects must not be receiving growth factors, except for erythropoietin

          -  Subjects with a "currently active" second malignancy, other than non-melanoma skin
             cancer, carcinoma in situ of the cervix, resected incidental prostate cancer (staged
             pT2 with Gleason score =< 6 and postoperative prostate-specific antigen [PSA] < 0.5
             ng/mL), or other adequately treated carcinoma-in-situ are ineligible; patients are not
             considered to have a "currently active" malignancy if they have completed therapy and
             are free of disease for >= 1 year

          -  Subjects with uncontrolled high blood pressure, unstable angina, symptomatic
             congestive heart failure (New York Heart Association [NYHA] class 3), myocardial
             infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not
             eligible

          -  Subjects with other severe concurrent disease which in the judgment of the
             investigator would make the patient inappropriate for entry into this study are
             ineligible

          -  Subjects must not have evidence of active leukemia in the central nervous system (CNS)

          -  Subjects must not have received any investigational agents within 30 days of study
             entry

          -  Subjects must not be pregnant or breastfeeding; pregnancy tests must be obtained for
             all females of child-bearing potential; pregnant or lactating patients are ineligible
             for this study; males or women of childbearing potential may not participate unless
             they have agreed to use an effective contraceptive method (defined as hormonal
             contraceptives, intrauterine devices, surgical contraceptives, or condoms)

          -  Subjects who have uncontrolled infection are not eligible; patients must have any
             active infections under control; fungal disease must be stable for at least 2 weeks
             before study entry

          -  Subjects with bacteremia must have documented negative blood cultures prior to study
             entry
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of grade 4, non-hematologic dose limiting toxicities assessed by National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0
Time Frame:Up to 2 years
Safety Issue:
Description:Data analysis will be descriptive. All estimates of dose-specific rates (e.g., response and toxicity) will be presented with corresponding confidence intervals using the exact method. The method of Atkinson and Brown will be used for any rate related to definition of dose limiting toxicity, due to two-stage sampling. The method of Conover will be used otherwise.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

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