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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Leukemia; Acute Myelogenous Leukemia
• Intervention / Treatment: Drug: Ciprofloxacin 750 MG; Drug: Etoposide; Drug: Ciprofloxacin 1000 MG; Drug: Ciprofloxacin 500 mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF Health Shands Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ciprofloxacin Dose Level 0	Drug: Ciprofloxacin 750 MG; 750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.; Other Names: Cipro; Drug: Etoposide; Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.; Other Names: Vepesid; VP-16
Experimental: Ciprofloxacin Dose Level +1	Drug: Etoposide; Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.; Other Names: Vepesid; VP-16; Drug: Ciprofloxacin 1000 MG; 1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.; Other Names: Cipro
Experimental: Ciprofloxacin Dose Level -1	Drug: Etoposide; Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.; Other Names: Vepesid; VP-16; Drug: Ciprofloxacin 500 mg; 500 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.; Other Names: Cipro

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Randall Brown, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2016
• Primary Completion (Actual): September 7, 2021
• Study Completion (Actual): November 15, 2021

Study Registration Dates

• First Submitted: May 12, 2016
• First Submitted That Met QC Criteria: May 13, 2016
• First Posted (Estimate): May 16, 2016

Study Record Updates

• Last Update Posted (Actual): August 5, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Etoposide; Ciprofloxacin
• Other Study ID Numbers: IRB201600693; UF-AML-CE-101 (Other Identifier: University of Florida); OCR14651 (Other Identifier: OF OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No