Study to Assess OPB-31121 in Advanced Leukemias or Myelodysplastic Syndromes

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. Read our disclaimer for details. Identifier: NCT01029509
Recruitment Status : Terminated (Colloborator-Sponsor decision to terminate.)
First Posted : December 10, 2009
Last Update Posted : July 23, 2012
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to find the highest tolerable dose of OPB-31121 that can be given to patients with leukemia or myelodysplastic syndrome (MDS).

Condition or disease Intervention/treatment Phase
Leukemia Drug: OPB 31121 Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Non-randomized Study to Assess the Pharmacokinetics, Dose Limiting Toxicity and Maximum Tolerated Dose of OPB-31121 in Subjects With Advanced Leukemias or Myelodysplastic Syndromes
Study Start Date : July 2008
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Arm Intervention/treatment
Experimental: OPB-31121
OPB-31121 200 mg twice daily for 21 days followed by 7 days of rest
Drug: OPB 31121
Starting dose of 200 mg (two 100 mg tablets) twice a day for 21 days followed by 7 days of rest.

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: Assessed at end of 28 day cycle for each dose cohort ]
    MTD defined as highest dose level at which < 2 of 6 subjects experience dose limiting toxicity (DLT) during the first cycle.

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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:

  1. Subjects with a diagnosis of treatment resistant or relapsed AML, ALL, or CLL for whom no standard treatment therapies are expected to result in durable remission. Subjects with advanced MDS should have failed lenalidomide or a hypomethylating agent. Subjects with CLL should have failed or relapsed after prior fludarabine and Campath. Subjects with CML should have previously exhausted standard therapy which provides clinical benefit. In addition, untreated subjects not eligible for standard therapy or unwilling to receive standard therapy with the above diagnosis will be eligible.
  2. Male and female subjects > / = 18 years of age
  3. Male and female subjects who are surgically sterile (ie, have undergone orchidectomy or hysterectomy, respectively); female subjects who have been postmenopausal for at least 24 consecutive months; or male and female subjects who agree to remain abstinent or to begin two acceptable methods of birth control from one week prior to drug administration through 30 days (for females) and 90 days (for males) from the last dose of study medication.
  4. (continued from #3) If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), condom, diaphragm, cervical cap or sponge with spermicide.
  5. Adequate liver function defined as </= 2.5 * institutional upper limit of normal (ULN), </= 2.5 * institutional ULN for alanine transaminase (ALT), aspartate transaminase, (AST) and bilirubin within normal limits unless Gilbert disease has been documented. .
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  7. In the absence of rapidly proliferative disease, a minimum of 2 weeks should elapse since prior standard or experimental therapy. Subjects must have recovered to grade less than or equal to 1 from any prior nonhematologic toxicities associated with any previous treatments. Use of leukopheresis or hydrea up to 48 hrs prior to the start of the study will be allowed in presence of proliferative disease. Use of hydrea will be permitted up to 5 days in each cycle for the control of proliferative disease.
  8. All eligible subjects must have received prior therapy (including chemotherapy, radiation therapy or surgery) greater than or equal to 2 weeks prior to study entry (Screening) and have recovered to Grade 1 toxicity from any prior non-hematological toxicity and to Grade 2 toxicity from any prior hematological toxicity except for thrombocytopenia defined as Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding following investigator's assessment of causality and positive relationship to study medication before participation in this trial.
  9. For CLL subjects only, all subjects with Rai Stages III-IV are eligible. For subjects with Rai stage 0-I disease, one or more indications for treatment as defined by the NCI sponsored Working Group must exist: • Massive or progressive splenomegaly; OR • Massive lymph nodes; nodal clusters, or progressive lymphadenopathy; OR • Grade 2 or 3 fatigue; or fever > / = 100.5° F or night sweats for greater than 2 weeks without documented infection; or presence of weight loss > / = 10% over the preceding 6 months;
  10. (continued from #9) OR • Progressive lymphocytosis with an increase in lymphocyte count of > / = 50% over a 2- month period or an anticipated doubling time of less than 6 months.
  11. For CML, subjects who have exhausted standard therapy which provides clinical benefit.
  12. Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the study.
  13. Subjects must have a life expectancy of > 3 months.
  14. Subjects must have a normal ejection fraction (>/= 50%) as measured by multiple gated acquisition (MUGA) scan.
  15. Subjects must have a normal serum creatinine (at baseline only) with a measured 24 hour creatinine clearance of > 60 cc/min.

Exclusion Criteria:

  1. Clinically significant condition in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the subject at risk or interfere with outcome variables.
  2. Subjects with active central nervous system (CNS) involvement by leukemia. Subjects with prior history of CNS disease will qualify if active disease is ruled out by imaging studies or spinal tap
  3. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  4. Subjects having taken an investigational drug or therapy within 14 days prior to dosing.
  5. Subjects who are pregnant or breast feeding. A negative serum pregnancy test must be confirmed prior to the first dose of study medication for WOCBP.
  6. Use of CYP3A4-enzyme inhibiting drugs and food; use of CYP3A4-enzyme inducing drugs and food; use of CYP2C9-enzyme inhibiting drugs; and use of CYP2C9 enzyme inducing drugs. Others: propranolol, lidocaine, propafenone, verapamil, nitroglycerin, and midazolam.
  7. Subjects with history of coagulopathy (or taking anticoagulants) including deep vein thrombosis (DVT)/ PE, unstable angina, myocardial infarction and stroke within the last 6 months.

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): NCT01029509

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Otsuka Pharmaceutical Co., Ltd.
Study Chair: Gautam Borthakur, MBBS UT MD Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01029509     History of Changes
Other Study ID Numbers: 2007-0488
First Posted: December 10, 2009    Key Record Dates
Last Update Posted: July 23, 2012
Last Verified: July 2012

Keywords provided by M.D. Anderson Cancer Center:
Advanced Leukemia
Acute myeloid leukemia
Chronic myeloid leukemia blast crisis
Acute lymphocytic leukemia
Chronic lymphocytic leukemia
Myelodysplastic syndromes
OPB 31121

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions