Clinical Trial: NCT03063944 - My Cancer Genome

NCT03063944

Description:

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 (refractory), has come back (relapsed), 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. Drugs used in chemotherapy, such as venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving STAT inhibitor OPB-111077, decitabine, and venetoclax may work better in treating patients with acute myeloid leukemia compared to decitabine alone.

Related Conditions:

Acute Myeloid Leukemia

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03063944

Trial Eligibility

Document

Title

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

Clinical Trial IDs

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

Conditions

Acute Myeloid Leukemia
Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia

Interventions

Drug	Synonyms	Arms
STAT Inhibitor OPB-111077	OPB-111077	Treatment (STAT inhibitor OPB-111077, venetoclax, decitabine)
Decitabine	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, 5-Aza-2''-deoxycytidine, 5-Azadeoxycytidine, Decitabine for Injection, Dezocitidine	Treatment (STAT inhibitor OPB-111077, venetoclax, decitabine)
Venetoclax	1257044-40-8, 4-(4-((2-(4-Chlorophenyl)-4, 4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide, ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto	Treatment (STAT inhibitor OPB-111077, venetoclax, decitabine)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of STAT inhibitor OPB-111077 (OPB-111077) in
      combination with decitabine and venetoclax.

      SECONDARY OBJECTIVES:

      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.

      OUTLINE: This is a dose escalation study of STAT inhibitor OPB-111077.

      INDUCTION CYCLE 1: Patients receive STAT inhibitor OPB-111077 orally (PO) once daily (QD) on
      days 1-28, and venetoclax PO QD on days 4-28 of cycle 1. Patients also receive decitabine
      intravenously (IV) over approximately 1 hour on days 4-8 of cycle 1. Patients who achieve
      complete remission (CR) after 1 cycle move on to Maintenance, and patients who do not achieve
      a CR move on to Cycle 2.

      INDUCTION CYCLE 2: Patients receive STAT inhibitor OPB-111077, venetoclax, and decitabine as
      in Induction Cycle 1. Patients who achieve CR, complete remission with incomplete hematologic
      recovery (CRi), partial remission (PR), or stable disease (or clinically significant
      hematologic improvement as determined by the investigator) move on to Maintenance.

      MAINTENANCE: Patients receive STAT inhibitor OPB-111077, venetoclax, and decitabine as in
      Induction Cycle 1. Cycles repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years.

Trial Arms

Name	Type	Description	Interventions
Treatment (STAT inhibitor OPB-111077, venetoclax, decitabine)	Experimental	INDUCTION CYCLE 1: Patients receive STAT inhibitor OPB-111077 PO QD on days 1-28, and venetoclax PO QD on days 4-28 of cycle 1. Patients also receive decitabine IV over approximately 1 hour on days 4-8 of cycle 1. Patients who achieve complete remission (CR) after 1 cycle move on to Maintenance, and patients who do not achieve a CR move on to Cycle 2. INDUCTION CYCLE 2: Patients receive STAT inhibitor OPB-111077, venetoclax, and decitabine as in Induction Cycle 1. Patients who achieve CR, CRi, PR, or stable disease (or clinically significant hematologic improvement as determined by the investigator) move on to Maintenance. MAINTENANCE: Patients receive STAT inhibitor OPB-111077, venetoclax, and decitabine as in Induction Cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	STAT Inhibitor OPB-111077 Decitabine Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologic evidence of high risk acute myeloid leukemia defined as
             one of the following:

               -  Non-M3 AML refractory to standard primary induction therapy

               -  Non-M3 AML relapsed after (i) any standard induction therapy (ii) any number of
                  standard or experimental salvage therapies

               -  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 clearance (CrCL) >= 45

          -  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 14 days or 5
             half-lives (whichever is longer) 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

          -  Subjects who are suitable for and willing to receive standard intensive induction
             therapy

          -  Subjects who are candidates for allogeneic transplantation, have a suitable donor, and
             are willing to undergo transplantation

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 5.0
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.

Secondary Outcome Measures

Measure:	Metabolomics as determined by bone marrow biopsy
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	Data analysis will be descriptive.

Measure:	Adenosine triphosphate (ATP) generation as determined by bone marrow biopsy
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	Data analysis will be descriptive.

Measure:	Apoptotic rate in blood and bone marrow assessed by apoptosis assays
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	Data analysis will be descriptive.

Measure:	Cellular proliferation in blood and bone marrow assessed by proliferation assays
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	Data analysis will be descriptive.

Measure:	Complete response as determined by bone marrow biopsy
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	Data analysis will be descriptive

Measure:	Complete response in the absence of total platelet recovery determined by bone marrow biopsy
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	Data analysis will be descriptive

Details

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

Last Updated

June 11, 2021

Clinical Trials /

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