Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)(UF-AML-CE-101)

Study Overview
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Brief Summary
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The purpose of the first part of this study is to establish the maximum tolerated dose (MTD) of oral ciprofloxacin when given in combination with a fixed dose of oral etoposide in patients with resistant acute myeloid leukemia (AML). The purpose of the second part of this study is to determine if the established dose of oral ciprofloxacin in combination with oral etoposide is effective in the treatment of patients with resistant AML.

Detailed Description
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This study will look at: any side effects that occur, the effectiveness of the study drug, and how your disease reacts to ciprofloxacin in combination with etoposide. This study will try to find the highest tolerated dose of ciprofloxacin without causing serious side effects. Ciprofloxacin is a commonly used antibiotic drug that is approved for use by the United States Food and Drug Administration (FDA). The FDA has not approved ciprofloxacin to treat AML. Etoposide is an anticancer chemotherapy drug that is approved for use by the FDA for the treatment of small cell lung cancer and testicular cancer. Etoposide is also used for treatment of various blood cancers. There is laboratory research that has shown that ciprofloxacin can make leukemia cells more sensitive to etoposide chemotherapy. This observation indicates that ciprofloxacin may help improve the effectiveness of etoposide in the treatment of resistant AML.

Official Title
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A Phase Ib/II Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)

Conditions
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Leukemia, Acute Myelogenous Leukemia, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Ciprofloxacin 750 MG
* Drug: Etoposide
* Drug: Ciprofloxacin 1000 MG
* Drug: Ciprofloxacin 500 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AML confirmed by review of bone marrow pathology at the University of Florida. Patients with relapsed and /or refractory AML who: failed to achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after at least one cycle of induction chemotherapy and not suitable for a second cycle of standard intensive chemotherapy; or who have progressed after 1 cycle of hypomethylating agent or intolerant to hypomethylating agent therapy and not suitable for standard induction chemotherapy regimens; or have relapsed after any duration of response. Per the treating physician, the subject must have a life expectancy of >= 4 weeks. Subject performance status must be Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2. Subject must have a total bilirubin <= 2 mg/dL and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 times the upper limit of normal. Subject must have serum creatinine < 2 mg/dL. Females of child-bearing potential may participate, provided they meet the following conditions: Must agree to use physician-approved contraceptive methods throughout the study and for 6 months following the last dose of ciprofloxacin and/or etoposide; Must have a negative serum pregnancy test within 7 days prior to beginning treatment on this study. Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods throughout the study and should avoid conceiving children for 6 months following the last dose of ciprofloxacin and/or etoposide. Must provide written informed consent and be willing to comply with all study-related procedures. Exclusion Criteria: History of allergic or significant adverse reaction [e.g., anaphylaxis, prolonged QTc, or severe tendonitis] to ciprofloxacin or etoposide. Acute promyelocytic leukemia (APL) with t(15;17). Prolonged baseline QTc, defined as QTc interval > 470 msec in women and > 450 msec in men, or > 480 msec in subjects with a bundle branch block. Uncontrolled, clinically significant infection. Subjects with a fever (temperature >= 38.3) thought to be related to leukemia are eligible assuming that blood cultures are negative during the 7 days prior to Cycle 1 Day 1 and there is no clinical evidence of active infection (e.g., negative or stable radiographs and negative physical examination). Ongoing, symptomatic Clostridium difficile infection. Subjects who are asymptomatic with negative stool for C. difficile may participate. Pregnant and or nursing. History of Myasthenia Gravis. Treatment with any anticancer therapy (standard or investigational) within 14 days prior to the first dose of ciprofloxacin or less than full recovery from the clinically significant toxic effects of that treatment. The use of hydroxyurea is allowed only during the first 14 days of Cycle 1.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciprofloxacin Dose Level 0<br> | Drug: Ciprofloxacin 750 MG<br>* 750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.<br>* Other names: Cipro;Drug: Etoposide<br>* Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.<br>* Other names: Vepesid;|
| Experimental: Ciprofloxacin Dose Level +1<br> | Drug: Etoposide<br>* Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.<br>* Other names: Vepesid;Drug: Ciprofloxacin 1000 MG<br>* 1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.<br>* Other names: Cipro;|
| Experimental: Ciprofloxacin Dose Level -1<br> | Drug: Etoposide<br>* Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.<br>* Other names: Vepesid;Drug: Ciprofloxacin 500 mg<br>* 500 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.<br>* Other names: Cipro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | Establish the maximum tolerated dose (MTD) of oral ciprofloxacin when given in combination with a fixed dose of oral Etoposide for the treatment of resistant AML. | 1 month | 
| Rate of Complete Remission | Determine the rate of complete remission (CR) following treatment with the MTD of oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. | 0 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Duration | Measure the response duration following treatment with oral ciprofloxacin in combination with oral etoposide for the treatment of resistant AML. | 111 days | 
| Progression-free Survival | Measure progression-free survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. | 317 days | 
| Overall Survival | Measure overall survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. | 317 days | 
| Percentage of Grade ≥ 3 Adverse Events | Estimate the rate of Grade ≥ 3 adverse events following treatment with oral ciprofloxacin and oral etoposide at the MTD. | 93 days |