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Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by JW Pharmaceutical
Sponsor:
Information provided by (Responsible Party):
JW Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01398462
First received: July 17, 2011
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

The small molecule, CWP232291, by binding Sam68 promotes apoptosis in selective cancer cells through 1)induction of the TNF-α apoptotic pathway, 2)alternative splicing, tipping the balance towards pro-apoptotic as opposed to anti-apoptotic isoforms, and 3)inhibition of the anti-apoptotic Wnt driven gene, survivin


Condition Intervention Phase
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
Myelofibrosis
Drug: CWP232291
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by JW Pharmaceutical:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Up to 3 weeks after start of injection ] [ Designated as safety issue: Yes ]
    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' [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose ] [ Designated as safety issue: No ]
    Peak Plasma Concentration (Cmax) of 'CWP232291'

  • AUC as a pharmacokinetic parameter of 'CWP232291' [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) of 'CWP232291'

  • 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 ] [ Designated as safety issue: No ]
    Peak Plasma Concentration (Cmax) of metabolites of 'CWP232291'

  • 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) of metabolites of 'CWP232291'


Estimated Enrollment: 48
Study Start Date: July 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CWP232291 Drug: CWP232291
IV Infusion

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01398462

Contacts
Contact: Hans de Haan, MD, PhD 1-858-449-1218 hans.dehaan@synteracthcr.com

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Animesh Pardanani, MBBS, PhD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Stefan H Faderl, MD         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Principal Investigator: John M Pagel, MD         
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Je-Hwan Lee, MD         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Chul-Won Jung, MD         
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Principal Investigator: Sung-Soo Yoon, MD         
Sponsors and Collaborators
JW Pharmaceutical
  More Information

No publications provided

Responsible Party: JW Pharmaceutical
ClinicalTrials.gov Identifier: NCT01398462     History of Changes
Other Study ID Numbers: JW-231A-101
Study First Received: July 17, 2011
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Primary Myelofibrosis
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on November 20, 2014