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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03063944
Recruitment Status : Recruiting
First Posted : February 24, 2017
Last Update Posted : December 8, 2020
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Brief Summary:
This phase I trial studies the side effects and best dose of STAT inhibitor OPB-111077 when given together with decitabine and venetoclax 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, decitabine and venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Drug: STAT Inhibitor OPB-111077 Drug: Decitabine Drug: Venetoclax Phase 1

Detailed Description:


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


I. To describe any preliminary efficacy of OPB-111077 in combination with decitabine and venetoclax 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 and venetoclax.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of OPB-111077 in Combination With Decitabine and Venetoclax for the Treatment of AML Refractory to or Ineligible for Intensive Chemotherapy
Actual Study Start Date : March 17, 2017
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2023

Arm Intervention/treatment
Experimental: Treatment (STAT inhibitor OPB-111077, decitabine)
Patients 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.
Drug: STAT Inhibitor OPB-111077
Given PO
Other Name: OPB-111077

Drug: Decitabine
Given IV
Other Names:
  • 127716
  • 2'-Deoxy-5-azacytidine
  • 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one
  • 2353-33-5
  • Dacogen
  • Deoxyazacytidine

Drug: Venetoclax
Given PO

Primary Outcome Measures :
  1. 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 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03063944

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Contact: Margaret Kasner, MD 215-955-5769

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United States, Pennsylvania
Sidney Kimmel Cancer Center at Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19171
Contact: Margaret Kasner, MD    215-955-5769      
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
Otsuka America Pharmaceutical
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Principal Investigator: Margaret Kasner, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
Additional Information:
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Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University Identifier: NCT03063944    
Other Study ID Numbers: 16C.773
First Posted: February 24, 2017    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors