Acute Myeloid Leukemia, in RelapsePhase 1NCT04402541
Study of CB-5339 in Acute Myeloid Leukemia or Myelodysplastic Syndrome
A Phase 1 study testing CB-5339 in people with Acute Myeloid Leukemia, in Relapse and Myelodysplastic Syndromes, run by Cleave Therapeutics, Inc. at 10 sites in 2 countries.
Trial summary
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapse, Myelodysplastic Syndromes
- What is being tested?
- CB-5339
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 8 Jun 2020to 23 Jul 2023
- 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
- Male or female and ≥ 18 years of age at the time of signing the consent form
- One of the following advanced hematologic malignancies including:
- Relapsed or refractory AML as defined by 2016 WHO criteria and are not candidates for curative therapies such as allogeneic hematopoietic cell transplant or for whom there is no standard of care therapy available that is likely to lead to disease remission according the investigator
- MDS high-very high risk by the revised international scoring system for evaluating prognosis in myelodysplastic syndromes that is recurrent or refractory or the participant is intolerant to established therapy known to provide clinical benefit for their condition (e.g., relapsed following treatment with hypomethylating agent or lack of response after > 4 cycles), according to treating physician. Potential participants who meet the criteria for intermediate risk may be considered with approval by the medical monitor if the participant has severe cytopenia(s) and/or elevated bone marrow blast counts.
- Adequate organ function defined as:
- Serum creatinine ≤1.5 mg/dL or an estimated glomerular filtration rate of ≥60 mL/min as calculated by the Cockcroft-Gault glomerular filtration rate equation
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- Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) unless considered due to Gilbert's disease or leukemic disease
- Aspartate aminotransferase (AST) ≤3 × the ULN; alanine aminotransferase (ALT) ≤3 × the ULN. Levels of AST and/or ALT ≤5 × the ULN may be acceptable for participants with known leukemic involvement of the liver after discussion with the study medical monitor
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If of childbearing potential, agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy during the study and 90 days after the last dose of CB-5339. Female participants of childbearing potential need a negative serum or urine pregnancy test within 7 days of study enrollment. Non-childbearing is defined as ≥ 1 year postmenopausal or surgically sterilized
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Who cannot join
- Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA).
- Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
- Participants with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Concomitant malignancy, requiring active treatment, except for basal-cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the uterine cervix, or localized prostate cancer.
- Adjuvant therapy for breast cancer or prostate cancer is allowed.
- Active, uncontrolled, systemic infection or severe localized infection during screening or prior to Cycle 1 Day 1 (C1D1; unless considered due to tumor by the investigator).
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- Note, participants receiving prophylactic anti-infectives are allowed on study.
- Known human immunodeficiency virus (HIV) infection with CD4+ T cell counts <350 cells/μL, initiation of antiretroviral therapy within 4 weeks before C1D1, or acquired immunodeficiency syndrome (AIDS)-related infection within 12 months before C1D1.
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the limit of quantification
- Major cardiac abnormalities as defined but not limited to the following: uncontrolled angina or unstable life-threatening arrhythmias, history of myocardial infarction within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association (NYHA) congestive heart failure, or left ventricular ejection fraction (LVEF) <45% as measured by echocardiogram (ECHO) within 28 days of C1D1
- Persistent (3 consecutive ECGs performed ≥5 minutes apart) prolongation of the corrected QT interval by Fredericia's method (QTcF) to > 480 msec
- Gastrointestinal conditions that may interfere with the absorption of orally-administered drugs including but not limited to short gut syndrome, gastroparesis, inflammatory bowel disease, or acute pancreatitis.
- Any other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or CB-5339 administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, may interfere with the interpretation of the study results and, in the Investigator's opinion, or would make the participant inappropriate for entry into this study
- A condition that is expected to require concomitant use of any medication listed as prohibited while on study.
- Known hypersensitivity to any components of CB-5339.
- Use of chemotherapy (except hydroxyurea), radiation or monoclonal antibodies within 14 days or 5 half-lives for small molecule inhibitors prior to first dose of CB-5339
- Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days of the first dose of CB-5339, or participants on immunosuppressive therapy post-HCT at the time of screening, use of calcineurin inhibitors within 4 weeks prior to first dose of CB-5339, or with clinically significant graft-versus-host disease (GVHD).
- Note: The use of topical steroids or <10mg oral prednisone for ongoing skin GVHD is permitted.
- Major surgery within 4 weeks prior to first dose of CB-5339. Participant must have recovered from surgery and be without current complications of infection or dehiscence
- Enrollment in other clinical trials unless approved by Medical Monitor
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States7 sites
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, 44122
KU Clinical Research Center
Fairway, Kansas, 66205
Saint Francis Hospital Cancer Center
Greenville, North Carolina, 29607
MD Anderson Cancer Cancer
Houston, Texas, 77030
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Weill Cornel Medical Center
New York, New York, 10065
Australia3 sites
St. Vincent Hospital, Sydney, NSW
Darlinghurst, New South Wales, 2010
Epworth Healthcare
Melbourne, Victoria, 3002
Haematology Clinical Trials Unit, Royal Perth Hospital
Perth, Western Australia, 6000
About this study
Official title: A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profiles of CB-5339 in Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Intermediate or High Risk Myelodysplastic Syndrome
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS.
Read the detailed description
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS. The study will include two parts:1) a Dose Escalation phase in participants with R/R AML, or R/R intermediate- to high-risk MDS and 2) a Dose Expansion phase in participants with R/R AML for whom there is no standard of care therapy available that is likely to lead to disease remission. Additional cohorts for participants with R/R intermediate- to high-risk MDS following hypomethylating agents or other AML cohorts may be added at a later time.
- Being tested
- CB-5339
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-5339Drug
Also called CB-5339 Tosylate
25mg and 75mg capsules
| Study group | Role | What they receive |
|---|---|---|
| CB-5339 | Experimental | Orally administered CB-5339 Receives: Drug: CB-5339 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Measured: 28 Days
Define the MTD and/or RP2D and schedule for CB-5339
Incidence and nature of DLTs with CB-5339 monotherapy for MTD determination. All available safety, efficacy and PK, for RP2D determination
Measured: 28 Days
Secondary outcomes (6)
Peak plasma concentration (Cmax)
Measured: Day 1 and Day 4
Time to reach peak plasma concentration (Tmax)
Measured: Day 1 and Day 4
Area under the plasma concentration time curve (AUC0-t)
Measured: Day 1 and Day 4
Elimination half-life (t½)
Measured: Day 1 and Day 4
Accumulation ratio
Measured: Day 1 and Day 4
Antitumor effects
CR/CRi rate at the RP2D in participants with R/R AML, as assessed by the investigator, based on 2017 ELN response criteria.
Objective response rate (ORR) at the RP2D in participants with R/R AML, as assessed by the investigator based on 2017 ELN response criteria.
DoCR in participants with R/R AML who attain CR or CRi
Measured: End of each cycle (cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start8 Jun 2020
- Primary completion23 Jul 2023
- Study completion23 Jul 2023
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 Leukemia, in RelapseStudies 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
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cleave Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Harris, Study chair, Cleave Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04402541
- Sponsor's protocol ID
- CTX-001
- Status last verified
- Aug 2023
- First submitted
- 18 May 2020
- Last updated
- 31 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wang F, Li S, Rosencrans WM, Cheng KW, Stott GM, Mroczkowski B, Chou TF. Sulforaphane is Synergistic with CB-5083 and Inhibits Colony Formation of CB-5083-Resistant HCT116 Cells. ChemMedChem. 2022 Jun 3;17(11):e202200030. doi: 10.1002/cmdc.202200030. Epub 2022 Apr 22.
PubMed 35451199
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profiles of CB-5339 in Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Intermediate or High Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT04402541
- Acronym / sponsor ID
- CTX-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Cleave Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Jun 2020 (actual)
- Primary completion
- 23 Jul 2023 (actual)
- Study completion
- 23 Jul 2023 (actual)
- First posted
- 27 May 2020 (actual)
- 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.
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS.
Detailed description
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS. The study will include two parts:1) a Dose Escalation phase in participants with R/R AML, or R/R intermediate- to high-risk MDS and 2) a Dose Expansion phase in participants with R/R AML for whom there is no standard of care therapy available that is likely to lead to disease remission. Additional cohorts for participants with R/R intermediate- to high-risk MDS following hypomethylating agents or other AML cohorts may be added at a later time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CB-5339 | Experimental | Drug: CB-5339Orally administered CB-5339 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female and ≥ 18 years of age at the time of signing the consent form
- One of the following advanced hematologic malignancies including:
- Adequate organ function defined as:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If of childbearing potential, agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy during the study and 90 days after the last dose of CB-5339. Female participants of childbearing potential need a negative serum or urine pregnancy test within 7 days of study enrollment. Non-childbearing is defined as ≥ 1 year postmenopausal or surgically sterilized
Key exclusion criteria (20 listed)
- Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA).
- Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
- Participants with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Concomitant malignancy, requiring active treatment, except for basal-cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the uterine cervix, or localized prostate cancer.
- Active, uncontrolled, systemic infection or severe localized infection during screening or prior to Cycle 1 Day 1 (C1D1; unless considered due to tumor by the investigator).
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 |
|---|---|---|
| CB-5339Also: CB-5339 Tosylate25mg and 75mg capsules | Drug | CB-5339 |
Primary outcome
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Time frame: 28 Days
Define the MTD and/or RP2D and schedule for CB-5339
Time frame: 28 Days
Incidence and nature of DLTs with CB-5339 monotherapy for MTD determination. All available safety, efficacy and PK, for RP2D determination
6 secondary outcomes
Peak plasma concentration (Cmax)
Time frame: Day 1 and Day 4
Time to reach peak plasma concentration (Tmax)
Time frame: Day 1 and Day 4
Area under the plasma concentration time curve (AUC0-t)
Time frame: Day 1 and Day 4
Elimination half-life (t½)
Time frame: Day 1 and Day 4
Accumulation ratio
Time frame: Day 1 and Day 4
Antitumor effects
Time frame: End of each cycle (cycle is 28 days)
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 31 Aug 2023.
- Derived from this study: PubMed 35451199Wang F, Li S, Rosencrans WM, Cheng KW, Stott GM, Mroczkowski B, Chou TF. Sulforaphane is Synergistic with CB-5083 and Inhibits Colony Formation of CB-5083-Resistant HCT116 Cells. ChemMedChem. 2022 Jun 3;17(11):e202200030. doi: 10.1002/cmdc.202200030. Epub 2022 Apr 22.
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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.
Scott Harris study chair
Cleave Therapeutics, Inc.
10 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 CB-5339 in people with Acute Myeloid Leukemia, in Relapse and Myelodysplastic Syndromes, run by Cleave Therapeutics, Inc. at 10 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 11 inclusion and 20 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 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Australia. 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?
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). (time frame: 28 Days). The study lists 2 primary outcomes in all. 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 NCT04402541, 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 31 Aug 2023.