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

Overview

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).

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2019

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.

Interventions

  • Drug: Phase 1 – OXi4503
    • Determination of MTD of OXi4503
  • Drug: Phase 1 – OXi4503 + cytarabine
    • Determination of MTD of the combination of OXi4503 + cytarabine
  • Drug: Phase 2 – OXi4503 + cytarabine
    • Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with AML
  • Drug: Phase 2 – OXi4503 + cytarabine
    • Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with MDS

Arms, Groups and Cohorts

  • Experimental: Phase 2 AML
    • OXi4503 at MTD plus cytarabine 1g/m2/day
  • Experimental: Phase 2 MDS
    • OXi4503 at MTD plus cytarabine 1g/m2/day
  • Experimental: OXi4503 dose escalation
    • MTD for OXi4503 will be determined
  • Experimental: OXi4503 + cytarabine dose escalation
    • MTD of the combination of OXi4503 + cytarbine will be determined

Clinical Trial Outcome Measures

Primary Measures

  • 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
  • Phase 2: Overall response rate of OXi4503 in combination with intermediate-dose cytarabine in subjects with MDS after failure of 1 prior hypomethylating agent (Arm A), and subjects with relapsed and refractory AML after treatment failure of up
    • Time Frame: 2 years

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mateon Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Rachel Couchenour, 650-635-7000

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