Acute Myeloid LeukemiaPhase 1NCT01398462
Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients
A Phase 1 study testing CWP232291 in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by JW Pharmaceutical at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- CWP232291
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Jul 2011to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
South Korea3 sites
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
United States2 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
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
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.
- Conditions
- Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Myelofibrosis
- Being tested
- CWP232291
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CWP232291Drug
IV Infusion
| Study group | Role | What they receive |
|---|---|---|
| CWP232291 | Experimental | Not described Receives: Drug: CWP232291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
If myelosuppression is DLT (Dose-Limiting Toxicity), it will be monitored up to 42 days after start of injection.
Measured: Up to 3 weeks after start of injection
Secondary outcomes (4)
Cmax as a pharmacokinetic parameter of 'CWP232291'
Peak Plasma Concentration (Cmax) of 'CWP232291'
Measured: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
AUC as a pharmacokinetic parameter of 'CWP232291'
Area under the plasma concentration versus time curve (AUC) of 'CWP232291'
Measured: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
Cmax as a pharmacokinetic parameter of metabolites of 'CWP232291'
Peak Plasma Concentration (Cmax) of metabolites of 'CWP232291'
Measured: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
AUC as a pharmacokinetic parameter of metabolites of 'CWP232291'
Area under the plasma concentration versus time curve (AUC) of metabolites of 'CWP232291'
Measured: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- JW Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01398462
- Sponsor's protocol ID
- JW-231A-101
- Status last verified
- Mar 2016
- First submitted
- 17 Jul 2011
- Last updated
- 8 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lee JH, Faderl S, Pagel JM, Jung CW, Yoon SS, Pardanani AD, Becker PS, Lee H, Choi J, Lee K, Kim M, Cortes JE. Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome. Blood Adv. 2020 May 12;4(9):2032-2043. doi: 10.1182/bloodadvances.2019000757.
PubMed 32396615
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01398462
- Acronym / sponsor ID
- JW-231A-101
- Conditions
- Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Myelofibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- JW PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 20 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CWP232291 | Experimental | Drug: CWP232291 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CWP232291IV Infusion | Drug | CWP232291 |
Primary outcome
Maximum Tolerated Dose
Time frame: 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.
4 secondary outcomes
Cmax as a pharmacokinetic parameter of 'CWP232291'
Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
AUC as a pharmacokinetic parameter of 'CWP232291'
Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 8, 24 hours post-dose
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2016.
- Derived from this study: PubMed 32396615Lee JH, Faderl S, Pagel JM, Jung CW, Yoon SS, Pardanani AD, Becker PS, Lee H, Choi J, Lee K, Kim M, Cortes JE. Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome. Blood Adv. 2020 May 12;4(9):2032-2043. doi: 10.1182/bloodadvances.2019000757.
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CWP232291 in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by JW Pharmaceutical at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Korea, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Up to 3 weeks after start of injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01398462, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2016.