Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients

Overview

About this study

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

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

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
  • 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Animesh Pardanani, MBBS, Ph.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20115498

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