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

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ClinicalTrials.gov Identifier: NCT02773732
Recruitment Status : Active, not recruiting
First Posted : May 16, 2016
Last Update Posted : August 17, 2021
Sponsor:
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE May 12, 2016
First Posted Date  ICMJE May 16, 2016
Last Update Posted Date August 17, 2021
Actual Study Start Date  ICMJE December 16, 2016
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE 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  ICMJE Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)(UF-AML-CE-101)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Acute Myelogenous Leukemia
  • Acute Myeloid Leukemia
Intervention  ICMJE
  • 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  ICMJE Experimental: Ciprofloxacin and Etoposide
Interventions:
  • Drug: Ciprofloxacin
  • Drug: Etoposide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 16, 2021)
11
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2016)
68
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02773732
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Randall Brown, MD University of Florida
PRS Account University of Florida
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP