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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04402541
Ethics application status
Date submitted
18/05/2020
Date registered
27/05/2020
Date last updated
5/05/2021

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 - Incidence and nature of DLTs with CB-5339 monotherapy for MTD determination. All available safety, efficacy and PK, for RP2D determination
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 - 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
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
Gender
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
N/A
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
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
Ohio
Country [5] 0 0
United States of America
State/province [5] 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
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.
Trial website
https://clinicaltrials.gov/show/NCT04402541
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
Scott Harris
Address 0 0
Country 0 0
Phone 0 0
(415) 562-8117
Fax 0 0
Email 0 0
sharris@cleavetherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04402541