Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients

Sponsor

JW Pharmaceutical (Industry)

Overall Status

Completed

CT.gov ID

NCT01398462

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

13.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Myelofibrosis	Drug: CWP232291	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

69 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2011

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CWP232291	Drug: CWP232291 IV Infusion

Arm

Intervention/Treatment

Experimental: CWP232291

Drug: CWP232291

IV Infusion

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose [Up to 3 weeks after start of injection]
If myelosuppression is DLT (Dose-Limiting Toxicity), it will be monitored up to 42 days after start of injection.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
2	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
3	Asan Medical Center	Seoul		Korea, Republic of
4	Samsung Medical Center	Seoul		Korea, Republic of
5	Seoul National University Hospital	Seoul		Korea, Republic of