Leukemia, Acute Myelogenous Leukemia, Acute Myeloid Leukemia
Conditions
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.
Interventions
750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.
DRUGEtoposide
Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
DRUGCiprofloxacin 1000 MG
1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.
500 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.
Sponsors
University of Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 1 month | 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. |
| Rate of Complete Remission | 0 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Duration | 111 days | Measure the response duration following treatment with oral ciprofloxacin in combination with oral etoposide for the treatment of resistant AML. |
| Progression-free Survival | 317 days | Measure progression-free survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. |
| Overall Survival | 317 days | Measure overall survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML. |
| Percentage of Grade ≥ 3 Adverse Events | 93 days | Estimate the rate of Grade ≥ 3 adverse events following treatment with oral ciprofloxacin and oral etoposide at the MTD. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin Dose Level 0 750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.
Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle. | 3 |
| Ciprofloxacin Dose Level +1 1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.
Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle. | 8 |
| Total | 11 |
Baseline characteristics
| Characteristic | Ciprofloxacin Dose Level 0 | Ciprofloxacin Dose Level +1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 5 Participants |
| Age, Continuous | 68.67 years | 61.75 years | 63.64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 8 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 7 Participants |
| Region of Enrollment United States | 3 participants | 8 participants | 11 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 7 / 8 |
| other Total, other adverse events | 3 / 3 | 7 / 8 |
| serious Total, serious adverse events | 2 / 3 | 4 / 8 |
Outcome results
Primary
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.
Time frame: 1 month
Population: 2 subjects were not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ciprofloxacin and Etoposide | Maximum Tolerated Dose | 1000 milligrams |
Primary
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.
Time frame: 0 months
Population: No participants were analyzed for this outcome measure because the study did not proceed to phase II.
Secondary
Overall Survival
Measure overall survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.
Time frame: 317 days
Population: 1 subject was still alive at the time protocol follow-up was discontinued, so they are not included in the analysis for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ciprofloxacin and Etoposide | Overall Survival | 140.67 days |
| Ciprofloxacin Dose Level +1 | Overall Survival | 109.29 days |
Secondary
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.
Time frame: 93 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ciprofloxacin and Etoposide | Percentage of Grade ≥ 3 Adverse Events | 20 percentage of reported adverse events |
| Ciprofloxacin Dose Level +1 | Percentage of Grade ≥ 3 Adverse Events | 28.45 percentage of reported adverse events |
Secondary
Progression-free Survival
Measure progression-free survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.
Time frame: 317 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ciprofloxacin and Etoposide | Progression-free Survival | 56 days |
| Ciprofloxacin Dose Level +1 | Progression-free Survival | 92.25 days |
Secondary
Response Duration
Measure the response duration following treatment with oral ciprofloxacin in combination with oral etoposide for the treatment of resistant AML.
Time frame: 111 days
Population: Only 1 participant in the ciprofloxacin Dose Level +1 cohort had a response to measure response duration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ciprofloxacin and Etoposide | Response Duration | 111 days |