Leukemia, Myelogenous, AcutePhase 1NCT01085656
A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory AML and MDS
A Phase 1 study testing OXi4503 in people with Leukemia, Myelogenous, Acute and Myelodysplastic Syndromes, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelogenous, Acute, Myelodysplastic Syndromes
- What is being tested?
- OXi4503
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Jan 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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;
- Active, uncontrolled, clinical significant infection;
- Any open wound;
- Pregnant and nursing patients are excluded because the effects of OXi4503 on a fetus or nursing child are unknown.
- Treatment with any anticancer therapy (standard or investigational) within the previous 21 days prior to the first dose of study drug or less than full recovery (CTCAE grade 1) from the clinically significant toxic effects of that treatment. The use of hydroxyurea may be used for two weeks after dosing in Cycle 1 (e.g., Days 1-14 dosed with hydroxyurea).
- Relative Exclusion Criteria:
- Patients on concurrent medications known to prolong the QTc interval may participate as long as their screening QTc interval meets eligibility criteria.
Trial locations and contacts
1 site in 1 country.
United States1 site
UF Health Shands Cancer Hopsital
Gainesville, Florida, 32608
About this study
Official title: A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS)
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.
Read the detailed description
Despite initial disease remissions with cytotoxic chemotherapies, patients with AML and MDS often relapse and die of their disease. Novel strategies for targeting dependent pathways are needed. AML and MDS depend on blood vessels for survival and proliferation. OXi4503 is a novel microtubule targeting agent that selectively destroys cancer-associated blood vessels, induces cancer cell apoptosis via an ortho-quinone moiety and results in significant regressions of solid tumors. OXi4503 is currently being tested in phase I clinical trials of advanced solid tumors. In preclinical studies with human AML, OXi4503 was cytotoxic to leukemia cells, decreased size of chloromas, regressed leukemic cell engraftment in bone marrow and brought about phenotypic and molecular remissions. Given these results, we hypothesize that OXi4503 has disease remitting effects in myeloid malignancies such as AML and MDS. Before evaluating efficacy, safety and maximum tolerated dose of OXi4503 will be defined in AML and MDS patients. In addition, assessments of pharmacokinetic (PK) and pharmacokinetic (PD) parameters will be made, and relationships between dose and biologic activity will be defined. Results from this trial will provide new clinical data and biologic insight regarding the effects of OXi4503 in AML and MDS, and will serve as the basis for future efficacy trials.
- Being tested
- OXi4503
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OXi4503Drug
Also called Combretastatin A1 Diphosphate, CA1P
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: OXi4503 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and establish the maximum tolerated dose (MTD) of OXi4503 in patients with relapsed and refractory AML and MDS.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2010 (estimated)
- Study startFeb 2011
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myelogenous, AcuteStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society
- Responsible party
- Sponsor
- Investigators
- Christopher R. Cogle, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01085656
- Sponsor's protocol ID
- UF OXi4503 AML MDS
- Status last verified
- Aug 2017
- First submitted
- 11 Mar 2010
- Last updated
- 8 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS)
- ClinicalTrials.gov ID
- NCT01085656
- Acronym / sponsor ID
- UF OXi4503 AML MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society
- Study start
- Feb 2011
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 12 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Despite initial disease remissions with cytotoxic chemotherapies, patients with AML and MDS often relapse and die of their disease. Novel strategies for targeting dependent pathways are needed. AML and MDS depend on blood vessels for survival and proliferation. OXi4503 is a novel microtubule targeting agent that selectively destroys cancer-associated blood vessels, induces cancer cell apoptosis via an ortho-quinone moiety and results in significant regressions of solid tumors. OXi4503 is currently being tested in phase I clinical trials of advanced solid tumors. In preclinical studies with human AML, OXi4503 was cytotoxic to leukemia cells, decreased size of chloromas, regressed leukemic cell engraftment in bone marrow and brought about phenotypic and molecular remissions. Given these results, we hypothesize that OXi4503 has disease remitting effects in myeloid malignancies such as AML and MDS. Before evaluating efficacy, safety and maximum tolerated dose of OXi4503 will be defined in AML and MDS patients. In addition, assessments of pharmacokinetic (PK) and pharmacokinetic (PD) parameters will be made, and relationships between dose and biologic activity will be defined. Results from this trial will provide new clinical data and biologic insight regarding the effects of OXi4503 in AML and MDS, and will serve as the basis for future efficacy trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OXi4503 | Experimental | Drug: OXi4503Dosing of OXi4503 will be an intravenous infusion (IV) over 10 minutes on Days 1, 8, 15, and 22 of each 28 day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must be at least 18 years of age;
- Patients must have either:
- 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;
Key exclusion criteria (21 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OXi4503Also: Combretastatin A1 Diphosphate, CA1PTwo 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. | Drug | OXi4503 |
Primary outcome
To determine the safety and establish the maximum tolerated dose (MTD) of OXi4503 in patients with relapsed and refractory AML and MDS.
Time frame: 28 days
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher R. Cogle, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OXi4503 in people with Leukemia, Myelogenous, Acute and Myelodysplastic Syndromes, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety and establish the maximum tolerated dose (MTD) of OXi4503 in patients with relapsed and refractory AML and MDS. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2017.