Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04402541




Registration number
NCT04402541
Ethics application status
Date submitted
18/05/2020
Date registered
27/05/2020
Date last updated
31/08/2023

Titles & IDs
Public title
Study of CB-5339 in Acute Myeloid Leukemia or Myelodysplastic Syndrome
Scientific 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
Secondary ID [1] 0 0
CTX-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia, in Relapse 0 0
Myelodysplastic Syndromes 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CB-5339

Experimental: CB-5339 - Orally administered CB-5339


Treatment: Drugs: CB-5339
25mg and 75mg capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Timepoint [1] 0 0
28 Days
Primary outcome [2] 0 0
Define the MTD and/or RP2D and schedule for CB-5339
Timepoint [2] 0 0
28 Days
Secondary outcome [1] 0 0
Peak plasma concentration (Cmax)
Timepoint [1] 0 0
Day 1 and Day 4
Secondary outcome [2] 0 0
Time to reach peak plasma concentration (Tmax)
Timepoint [2] 0 0
Day 1 and Day 4
Secondary outcome [3] 0 0
Area under the plasma concentration time curve (AUC0-t)
Timepoint [3] 0 0
Day 1 and Day 4
Secondary outcome [4] 0 0
Elimination half-life (t½)
Timepoint [4] 0 0
Day 1 and Day 4
Secondary outcome [5] 0 0
Accumulation ratio
Timepoint [5] 0 0
Day 1 and Day 4
Secondary outcome [6] 0 0
Antitumor effects
Timepoint [6] 0 0
End of each cycle (cycle is 28 days)

Eligibility
Key inclusion criteria
1. Male or female and = 18 years of age at the time of signing the consent form
2. 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.
3. 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
* 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
4. Eastern Cooperative Oncology Group (ECOG) performance status =2.
5. 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
6. 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA).
2. 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.
3. Participants with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
4. 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.
5. 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).

• Note, participants receiving prophylactic anti-infectives are allowed on study.
6. 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.
7. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the limit of quantification
8. 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
9. Persistent (3 consecutive ECGs performed =5 minutes apart) prolongation of the corrected QT interval by Fredericia's method (QTcF) to > 480 msec
10. 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.
11. 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
12. A condition that is expected to require concomitant use of any medication listed as prohibited while on study.
13. Known hypersensitivity to any components of CB-5339.
14. 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
15. 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.
16. 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
17. Enrollment in other clinical trials unless approved by Medical Monitor

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/07/2023
Sample size
Target
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
St. Vincent Hospital, Sydney, NSW - Darlinghurst
Recruitment hospital [2] 0 0
Epworth Healthcare - Melbourne
Recruitment hospital [3] 0 0
Haematology Clinical Trials Unit, Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3002 - Melbourne
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cleave Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Scott Harris
Address 0 0
Cleave Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04402541