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

NCT02773732 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB201600693UF-AML-CE-101OCR14651
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Acute Myelogenous Leukemia; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Response Duration

  111 days

• Progression-free Survival

  317 days

• Overall Survival

  317 days

• Percentage of Grade ≥ 3 Adverse Events

  93 days

Study Arms (3)

Ciprofloxacin Dose Level 0

EXPERIMENTAL

Drug: Ciprofloxacin 750 MG; Drug: Etoposide

Ciprofloxacin Dose Level +1

EXPERIMENTAL

Drug: Etoposide; Drug: Ciprofloxacin 1000 MG

Ciprofloxacin Dose Level -1

EXPERIMENTAL

Drug: Etoposide; Drug: Ciprofloxacin 500 mg

Interventions

Ciprofloxacin 750 MG DRUG

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

Also known as: Cipro

Ciprofloxacin Dose Level 0

Etoposide DRUG

Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.

Also known as: VP-16, Vepesid

Ciprofloxacin Dose Level +1; Ciprofloxacin Dose Level -1; Ciprofloxacin Dose Level 0

Ciprofloxacin 1000 MG DRUG

1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.

Also known as: Cipro

Ciprofloxacin Dose Level +1

Ciprofloxacin 500 mg DRUG

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

Also known as: Cipro

Ciprofloxacin Dose Level -1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

UF Health Shands Cancer Hospital

Gainesville, Florida, 32608, United States

Location

Related Publications (1)

• Gera K, Cline C, Al-Mansour Z, Medvec A, Lee JH, Galochkina Z, Hsu J, Hiemenz J, Farhadfar N, Dean EA, Wingard JR, Brown R. A phase ib clinical trial of oral ciprofloxacin and etoposide in subjects with resistant acute myeloid leukemia. Leuk Lymphoma. 2024 Oct;65(10):1502-1510. doi: 10.1080/10428194.2024.2361111. Epub 2024 Jun 6.

  PMID: 38841781 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute

Interventions

Ciprofloxacin; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Allison Allegra
• Organization: University of Florida

allisonallegra3@ufl.edu

352-294-5691

Study Officials

• Randall Brown, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 16, 2016
• Study Start: December 16, 2016
• Primary Completion: September 7, 2021
• Study Completion: November 15, 2021
• Last Updated: August 5, 2022
• Results First Posted: August 5, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)