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 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.
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
| Drug | Synonyms | Arms |
|---|
| STAT Inhibitor OPB-111077 | OPB-111077 | Treatment (STAT inhibitor OPB-111077, 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 | Treatment (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
| Name | Type | Description | Interventions |
|---|
| Treatment (STAT inhibitor OPB-111077, decitabine) | Experimental | 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. | - 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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