Clinical Trials /

Dose Escalation of OXi4503 as Single Agent and Combination With Cytarabine w/Subsequent Ph 2 Cohorts for AML and MDS

NCT02576301

Description:

Phase 1 will investigate maximum tolerated dose of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS. Phase 2 will investigate overall response rate of OXi4503 in combination with intermediate-dose cytarabine in 1) subjects with MDS after failure of 1 prior hypomethylating agent (Arm A) and 2) subjects with relapsed and refractory AML after treatment failure of up to 1 prior chemotherapy regimen (Arm B).

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation of OXi4503 as Single Agent and Combination With Cytarabine w/Subsequent Ph 2 Cohorts for AML and MDS
  • Official Title: Ph 1b Dose Escalation Study of OXi4503 as a Single Agent and in Combination With Cytarabine With Subsequent Phase 2 Cohorts for Subjects With Relapsed/Refractory Acute AML and MDS

Clinical Trial IDs

  • ORG STUDY ID: OX1222
  • NCT ID: NCT02576301

Conditions

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
Phase 1 - OXi4503CA1P, combretastatin A1-diphosphateOXi4503 dose escalation
Phase 1 - OXi4503 + cytarabineCA1P, combretastatin A1-diphosphateOXi4503 + cytarabine dose escalation
Phase 2 - OXi4503 + cytarabineCA1P, combretastatin A1-diphosphatePhase 2 AML
Phase 2 - OXi4503 + cytarabineCA1P, combretastatin A1-diphosphatePhase 2 MDS

Purpose

Phase 1 will investigate maximum tolerated dose of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS. Phase 2 will investigate overall response rate of OXi4503 in combination with intermediate-dose cytarabine in 1) subjects with MDS after failure of 1 prior hypomethylating agent (Arm A) and 2) subjects with relapsed and refractory AML after treatment failure of up to 1 prior chemotherapy regimen (Arm B).

Detailed Description

      Phase 1 dose escalation component will assess the safety, PK/PD, and preliminary efficacy of
      OXi4503 as a single agent in subjects with relapsed/refractory AML and MDS, and the safety
      and PK/PD of the combination of OXi4503 with intermediate-dose cytarabine in subjects with
      AML/MDS.

      Phase 2 will assess the preliminary efficacy of the OXi4503+cytarabine combination in 2
      cohorts.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 2 AMLExperimentalOXi4503 at MTD plus cytarabine 1g/m2/day
  • Phase 2 - OXi4503 + cytarabine
Phase 2 MDSExperimentalOXi4503 at MTD plus cytarabine 1g/m2/day
  • Phase 2 - OXi4503 + cytarabine
OXi4503 dose escalationExperimentalMTD for OXi4503 will be determined
  • Phase 1 - OXi4503
OXi4503 + cytarabine dose escalationExperimentalMTD of the combination of OXi4503 + cytarbine will be determined
  • Phase 1 - OXi4503 + cytarabine

Eligibility Criteria

        Inclusion Criteria:

          1. Provide informed consent

          2. ≥ 18 years of age

          3. Phase 1 (dose escalation) subjects must have either:

               -  AML that has failed to achieve complete remission or morphologic complete
                  remission or

               -  MDS - Marrow blasts must be > 5% and disease failed at least 1 prior
                  hypomethylating agent

          4. Phase 2 (expansion) subjects must have either MDS or relapsed/refractory AML

          5. Eastern Cooperative Oncology Group performance status 0, 1, or 2

          6. Total bilirubin ≤ 2

          7. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5
             times upper limit of normal (ULN)

          8. Serum creatinine < 2.5 times ULN

          9. Prothrombin time (PT)/international normalized ratio and (PTT) in normal range ± 25%

         10. Women of child-bearing potential

         11. Males with female partners of child-bearing potential must agree to use
             physician-approved contraceptive methods

        Exclusion Criteria:

          1. Acute promyelocytic leukemia

          2. Absolute peripheral blood myeloblast count greater than 20,000/mm3

          3. Uncontrolled hypertension

          4. History of congenital long QT syndrome or torsades de pointes

          5. Pathologic bradycardia or heart block

          6. Prolonged baseline QTc

          7. Hiistory of ventricular arrhythmia

          8. Myocardial infarction and/or new ST elevation

          9. Any history of hemorrhagic stroke

         10. Symptomatic congestive heart failure

         11. Major hemorrhagic event within 28 days

         12. Suggestive central nervous system involvement with leukemia

         13. Any open wound

         14. Pregnant and nursing subjects are excluded

         15. Treatment with any anticancer therapy

         16. Treatment with colchicine is excluded.

         17. Psychiatric disorders that would interfere with consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b:MTD of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mateon Therapeutics

Trial Keywords

  • AML
  • MDS

Last Updated

June 1, 2018