Clinical Trials /

Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients

NCT01398462

Description:

CWP232291 blocks proliferation of cancer cells via activation of caspases. Active caspase have been shown to target beta-catenin, the hallmark of canonical Wnt signaling, for degradation through caspase-directed cleavage. CWP232291 targets beta-catenin for degradation and thereby inhibits the expression of cell cycle and anti-apoptotic genes such as cyclin D1 and survivin.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients
  • Official Title: A Phase I Clinical Study of CWP232291 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia-2, Myelodysplastic Syndrome Having Failed Hypomethylating Treatment, and High-Risk Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: JW-231A-101
  • NCT ID: NCT01398462

Conditions

  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome
  • Myelofibrosis

Interventions

DrugSynonymsArms
CWP232291CWP232291

Purpose

CWP232291 blocks proliferation of cancer cells via activation of caspases. Active caspase have been shown to target beta-catenin, the hallmark of canonical Wnt signaling, for degradation through caspase-directed cleavage. CWP232291 targets beta-catenin for degradation and thereby inhibits the expression of cell cycle and anti-apoptotic genes such as cyclin D1 and survivin.

Trial Arms

NameTypeDescriptionInterventions
CWP232291Experimental
  • CWP232291

Eligibility Criteria

        Inclusion Criteria:

          -  Able to understand and willing to sign an informed consent form (ICF) prior to
             initiation of any study-specific procedure and treatment

          -  18 years of age

          -  3. A pathologically confirmed diagnosis of AML or CMML-2 by World Health Organization
             (WHO) classification that is relapsed or refractory or for which no current therapies
             are anticipated to result in a durable remission, or MDS by WHO classification are
             RAEB-1 or RAEB-2 and that have failed at least three cycles of hypomethylating
             therapy, or primary (PMF), post-polycythemia vera (PPMF) or post-essential
             thrombocythemia (PTMF) MF by WHO classification, are high-risk category by the Dynamic
             International Prognostic Scoring System (DIPSS Plus), have ≥1% circulating blasts, and
             have failed treatment with ruxolitinib

          -  Eastern Cooperative Oncology Group (ECOG) performance score 0-2

          -  In the absence of rapidly progressing disease, the interval from prior treatment to
             time of study drug administration should be at least 2 weeks for cytotoxic agents or
             at least 5 half-lives for noncytotoxic agents. If a patient is on hydroxyurea to
             control peripheral blood leukemic cell counts, the patient must have discontinued
             hydroxyurea for at least 24 hours before initiation of treatment with study drug.
             Persistent clinically significant toxicities from prior chemotherapy must not be
             greater than grade 1

          -  Adequate renal function:

               -  Serum creatinine =/< 2.0mg/dL

          -  Adequate hepatic function:

               -  Total bilirubin <1.5 x upper limit of normal (ULN), unless considered due to
                  Gilbert's syndrome

               -  Alkaline phosphatase (AP) =/< 2.5 x ULN

               -  Aspartate transaminase (AST) or alanine transaminase (ALT) ≤3 x ULN, unless
                  considered due to organ leukemic involvement

          -  Women of child-bearing potential (i.e., women who are pre menopausal or not surgically
             sterile) must use acceptable contraceptive methods (abstinence, intrauterine device
             [IUD], oral contraceptive, or double barrier device), and must have a negative serum
             or urine pregnancy test within 2 weeks prior to beginning treatment on this trial.
             Sexually active men must also use acceptable contraceptive methods for the duration of
             time on study

          -  Able to adhere to the study visit schedule and other protocol requirements

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including, but not limited to, uncontrolled
             infection, symptomatic congestive heart failure (CHF), cardiac arrhythmia, or
             psychiatric illness/social situation that would limit compliance with study
             requirements

          -  Active heart disease including myocardial infarction (MI) within previous 3 months,
             symptomatic coronary artery disease (CAD), arrhythmias not controlled by medication,
             or uncontrolled CHF

          -  Active central nervous system (CNS) disease

          -  Therapy with any other standard or investigational treatment for hematologic
             malignancy (except hydroxyurea, as mentioned in the inclusion criteria)

          -  Therapy with anticoagulant or antithrombotic agents (including aspirin) within 7 days
             prior to study drug administration

          -  History of gastrointestinal (GI) hemorrhage

          -  Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B
             or C

          -  Pregnant or nursing women. Pregnant and nursing patients are excluded because the
             effects of CWP232291 on a fetus or nursing child are unknown.

          -  Patients eligible for bone marrow transplant, regardless of age

          -  Patients with FLT3 ITD positive AML or AML patients with other cytogenetic
             abnormalities who are eligible for trials of other targeted investigational agents
             from which the investigator feels there is greater benefit.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:Up to 3 weeks after start of injection
Safety Issue:
Description:If myelosuppression is DLT (Dose-Limiting Toxicity), it will be monitored up to 42 days after start of injection.

Secondary Outcome Measures

Measure:Cmax as a pharmacokinetic parameter of 'CWP232291'
Time Frame:0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
Safety Issue:
Description:Peak Plasma Concentration (Cmax) of 'CWP232291'
Measure:AUC as a pharmacokinetic parameter of 'CWP232291'
Time Frame:0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
Safety Issue:
Description:Area under the plasma concentration versus time curve (AUC) of 'CWP232291'
Measure:Cmax as a pharmacokinetic parameter of metabolites of 'CWP232291'
Time Frame:0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
Safety Issue:
Description:Peak Plasma Concentration (Cmax) of metabolites of 'CWP232291'
Measure:AUC as a pharmacokinetic parameter of metabolites of 'CWP232291'
Time Frame:0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
Safety Issue:
Description:Area under the plasma concentration versus time curve (AUC) of metabolites of 'CWP232291'

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:JW Pharmaceutical

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