Clinical Trials /

Study of CB-5339 in Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT04402541

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of CB-5339 in Acute Myeloid Leukemia or Myelodysplastic Syndrome
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CTX-001
  • NCT ID: NCT04402541

Conditions

  • Acute Myeloid Leukemia, in Relapse
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
CB-5339CB-5339 TosylateCB-5339

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
CB-5339ExperimentalOrally administered CB-5339
  • CB-5339

Eligibility Criteria

        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

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Time Frame:28 Days
Safety Issue:
Description:Incidence and nature of DLTs with CB-5339 monotherapy for MTD determination. All available safety, efficacy and PK, for RP2D determination

Secondary Outcome Measures

Measure:Peak plasma concentration (Cmax)
Time Frame:Day 1 and Day 4
Safety Issue:
Description:
Measure:Time to reach peak plasma concentration (Tmax)
Time Frame:Day 1 and Day 4
Safety Issue:
Description:
Measure:Area under the plasma concentration time curve (AUC0-t)
Time Frame:Day 1 and Day 4
Safety Issue:
Description:
Measure:Elimination half-life (t½)
Time Frame:Day 1 and Day 4
Safety Issue:
Description:
Measure:Accumulation ratio
Time Frame:Day 1 and Day 4
Safety Issue:
Description:
Measure:Antitumor effects
Time Frame:End of each cycle (cycle is 28 days)
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cleave Therapeutics, Inc.

Last Updated

July 7, 2020