A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory AML and MDS

NCT01085656 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: UF OXi4503 AML MDS
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is intended to determine the safety and maximum tolerated dose of a drug, OXi4503 (combretastatin A1 diphosphate, CA1P, OXiGENE), in patients with relapsed and refractory AML and MDS.

Conditions

Leukemia, Myelogenous, Acute; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• To determine the safety and establish the maximum tolerated dose (MTD) of OXi4503 in patients with relapsed and refractory AML and MDS.

  28 days

Study Arms (1)

OXi4503

EXPERIMENTAL

Dosing of OXi4503 will be an intravenous infusion (IV) over 10 minutes on Days 1, 8, 15, and 22 of each 28 day cycle.

Drug: OXi4503

Interventions

OXi4503 DRUG

Two safety cohorts treating two (2) patients at a dose of 2.5 mg/m2 followed by two patients at 3.75 mg/m2 will be completed prior to beginning at the dose level of 5 mg/m2. Dosing of OXi4503 will be an intravenous infusion (IV) over 10 minutes on Days 1, 8, 15, and 22 of each 28 day cycle. Dose escalations and de-escalations of 25% will be made until the maximum tolerated dose is reached. Number of cycles: After Cycle 1, subjects who achieve stable disease (SD) or greater response may continue to receive additional cycles of treatment until either disease progression (defined as greater than 25% increase in leukemia myeloblasts in the bone marrow compared to baseline examination) or unacceptable toxicity due to the investigational agent.

Also known as: Combretastatin A1 Diphosphate, CA1P

OXi4503

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least 18 years of age;
• Patients must have either:
• AML (de novo or secondary, and any WHO 2008 classification excluding acute promyelocytic leukemia) that has failed to achieve CR or CRi (IWG 2003) after at least 1 cycle of induction chemotherapy, or has relapsed after any duration of CR or CRi; or,
• MDS (RAEB-1 or RAEB-2 WHO 2008 classification) that has failed to achieve any hematologic improvement (IWG 2006 criteria) after at least 4 cycles of induction therapy (e.g., azacitidine, decitabine), or has relapsed after any duration of CR or PR.;
• Patient performance status must be Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2;
• Patients must have a life expectancy of greater than 14 days;
• Patients must have total bilirubin ≤ 2;
• Patients must have serum AST and ALT levels ≤ 2.5 times upper limit of normal;
• Patients must have serum creatinine less than or equal to 2.5 times upper limit of normal;
• Patients must have PT/INR and PTT in normal range ± 25%;
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) may participate, provided they meet the following conditions:
• Must agree to use physician-approved contraceptive methods (e.g., abstinence, intrauterine device, oral contraceptive, double barrier device) throughout the study and for three months following the last dose of OXi4503; and
• Must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this trial;
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 6 months following the last dose of OXi4503;
• Written informed consent, willingness, and ability to comply with all study procedures.

You may not qualify if:

• Acute promyelocytic leukemia (APL) with t(15;17);
• Absolute peripheral blood myeloblast count greater than 25,000/mm3;
• Uncontrolled hypertension, defined as blood pressure 140/90 mm Hg despite maximum medical intervention;
• History of congenital long QT syndrome or torsades de pointes;
• Pathologic bradycardia or heart block (excluding first degree heart block);
• Prolonged baseline QTc, defined as QTc interval \> 470 msec in women and \> 450 msec in men;
• History of ventricular arrhythmia (excluding premature ventricular contractions, PVCs);
• Major operative surgery within 28 days;
• Unstable angina pectoris within 28 days;
• Myocardial infarction and/or new ST elevation or depression or new Q wave on ECG within 28 days;
• Any history of hemorrhagic stroke;
• Symptomatic congestive heart failure Class III or greater (New York Heart Association Functional Classification);
• On full dose anti-coagulation defined as warfarin intended to raise the INR to 2-3, or enoxaparin 1 mg/kg twice a day or unfractionated heparin intended to raise the PTT to 60-90 seconds;
• Major hemorrhagic event within 28 days requiring transfusion of packed red blood cells;
• Prior history of hypertensive crisis or hypertensive encephalopathy;

Sponsors & Collaborators

• University of Florida: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (1)

UF Health Shands Cancer Hopsital

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Oxi 4503

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Christopher R. Cogle, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: March 12, 2010
• Study Start: February 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: August 8, 2017

Record last verified: 2017-08

Locations

US (1)