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

• ClinicalTrials.gov Identifier: NCT02773732
• Recruitment Status: Recruiting
• First Posted: May 16, 2016
• Last Update Posted: October 8, 2020
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Tracking Information

• First Submitted Date: May 12, 2016
• First Posted Date: May 16, 2016
• Last Update Posted Date: October 8, 2020
• Actual Study Start Date: December 16, 2016
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2016)

• 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. [ Time Frame: 1 month ]
• 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. [ Time Frame: 24 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 13, 2016)

• Measure the response duration following treatment with oral ciprofloxacin in combination with oral etoposide for the treatment of resistant AML. [ Time Frame: 24 months ]
• Measure progression-free survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. [ Time Frame: 24 months ]
• Measure overall survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. [ Time Frame: 24 months ]
• Estimate the incidence of Grade ≥ 3 adverse events following treatment with oral ciprofloxacin and oral etoposide at the MTD. [ Time Frame: 24 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: May 13, 2016)

• Serum concentration of ciprofloxacin on Day 8 of treatment at each dose level. [ Time Frame: Day 8 ]
• Peak plasma concentration (Cmax) of oral ciprofloxacin on day 8 of treatment at each dose level. [ Time Frame: Day 8 ]
• The lowest (trough) concentration (Cmin) of oral ciprofloxacin on day 8 of treatment at each dose level. [ Time Frame: Day 8 ]
• Area under the curve (AUC) of oral ciprofloxacin on day 8 of treatment at each dose level. [ Time Frame: Day 8 ]
• Elimination half life (T1/2) of oral ciprofloxacin on day 8 of treatment at each dose level. [ Time Frame: Day 8 ]
• Number of participants with changes in chromosomal karyotype following treatment with oral ciprofloxacin and oral Etoposide for the treatment of resistant AML. [ Time Frame: 24 months ]
• Number of participants with changes in common somatic mutations following treatment with oral ciprofloxacin and oral Etoposide for the treatment of resistant AML. [ Time Frame: 24 months ]

Descriptive Information

• Brief Title: Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)(UF-AML-CE-101)
• Official Title: A Phase Ib/II Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)
• Brief Summary: 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

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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia

Intervention

• Drug: Ciprofloxacin

  Ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.

  Dose Level 0 Ciprofloxacin 750 mg Dose Level +1 Ciprofloxacin 1000 mg Dose Level -1 Ciprofloxacin 500 mg

  Other Name: Cipro
• Drug: Etoposide
  Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
  Other Names:

  • VP-16
  • Vepesid

Study Arms

Experimental: Ciprofloxacin and Etoposide

Interventions:

• Drug: Ciprofloxacin
• Drug: Etoposide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 13, 2016): 68
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Erin Monari, PhD; (352) 273-8128; PMO@cancer.ufl.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02773732
• Other Study ID Numbers: IRB201600693; UF-AML-CE-101 ( Other Identifier: University of Florida ); OCR14651 ( Other Identifier: OF OnCore )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Florida
• Study Sponsor: University of Florida
• Collaborators: Not Provided

Investigators

• Principal Investigator: Randall Brown, MD; University of Florida

• PRS Account: University of Florida
• Verification Date: October 2020