Acute Myeloid Leukemia
Conditions
Keywords
AML, clofarabine, cytarabine, persistent AML, induction therapy
Brief summary
The combination of clofarabine and cytarabine is an effective and reasonably well-tolerated treatment regimen in patients with either relapsed/refractory or newly diagnosed AML. For this prospective study, we propose the use of clofarabine and cytarabine for second course induction therapy for patients with persistent AML after treatment with an anthracycline and cytarabine.
Detailed description
The primary objective of this prospective study is to evaluate the efficacy (i.e., complete response rate) of clofarabine and cytarabine as second course therapy for the treatment of AML. The secondary objectives are to assess the treatment-related toxicities, to determine the overall and relapse-free survival for patients with AML who are treated with this regimen, and to evaluate potential factors that are predictive of response. The investigational nature and objective of this study, the procedures involved and their associated risks, potential benefits, and potential alternative therapies will be explained to the patient, and a signed informed consent document will be obtained. Once consented, eligible patients will be treated by the acute leukemia service on the University of Pittsburgh Cancer Institute inpatient unit. Prior to the start of chemotherapy, patients will receive dexamethasone and ondansetron as pre-medication. Clofarabine will then be administered as intravenous infusion on days 1 through 5. Patients will be monitored closely with vital signs. Cytarabine will then be given as intravenous infusion, starting 3 (maximum of 4) hours after the completion of clofarabine administration on days 1 through 5.
Interventions
DRUGClofarabine
Clofarabine will be administered as a 1-hour (range: 1 hour minimum to 2 hours maximum) intravenous infusion at a dose of 40mg/m2 daily on days 1 through 5.
DRUGCytarabine
Cytarabine at a dose of 1g/m2 daily will be given as a 2-hour intravenous infusion, starting 3 hours after the completion of clofarabine administration on days 1 through 5.
Sponsors
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with newly diagnosed AML based on the World Health Organization classification who have persistent disease after their first course treatment with an anthracycline and cytarabine 2. Able to understand and have the ability to provide written informed consent 3. Patients over 18 years of age 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 5. Left ventricular ejection fraction (LVEF) ≥ 50% 6. Negative urine pregnancy test for all females 7. All subjects must agree to use an effective method of contraception while receiving the study drugs
Exclusion criteria
1. Diagnosis of acute promyelocytic leukemia 2. Relapsed AML 3. Prior use of clofarabine 4. Previous allogeneic or autologous hematopoietic cell transplantation 5. Impaired liver function (serum total bilirubin \> 2.0 mg/dL, alanine aminotransferase and aspartate aminotransferase ≥ 4 x the upper limit of normal) 6. Impaired renal function (serum creatinine ≥ 2.0 mg/dL) 7. Uncontrolled or life-threatening infection that is not responding to antimicrobial therapy 8. History of a psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent 9. Concurrent active malignancy; exceptions include patients who have been disease free for 5 years, patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or patients with another malignancy that is indolent or definitively treated 10. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory or cardiac disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clinical Response | Between 14 and 28 days from start of study treatment | Number of patients with newly diagnosed Acute Myeloid Leukemia who achieved Complete Response to therapy as determined by bone marrow biopsy evaluation. A CR designation required that the patient achieved a morphologic leukemia-free state and an absolute neutrophil count greater than or equal to 1.0 x 10\^9/l, a platelet count greater than or equal to 100 x 10\^9/l, and no evidence of extramedullary disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 24 months | Number of months of survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m\^2/Day) + Cytarabine (1g/m\^2/Day). |
| Relapse Free Survival | Up to 24 months | Number of months of relapse free survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m\^2/Day) + Cytarabine (1g/m\^2/Day). |
| Predictive Factors for Response to Treatment. | Up to 1 year | Evaluation of potential factors that are predictive of clinical response in newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m\^2/Day) + Cytarabine (1g/m\^2/Day). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day) Patients with newly diagnosed Acute Myeloid Leukemia who received clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m\^2 daily plus cytarabine at a dose of 1g/m\^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day) |
|---|---|
| Age, Continuous | 55 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
Complete Clinical Response
Number of patients with newly diagnosed Acute Myeloid Leukemia who achieved Complete Response to therapy as determined by bone marrow biopsy evaluation. A CR designation required that the patient achieved a morphologic leukemia-free state and an absolute neutrophil count greater than or equal to 1.0 x 10\^9/l, a platelet count greater than or equal to 100 x 10\^9/l, and no evidence of extramedullary disease.
Time frame: Between 14 and 28 days from start of study treatment
Population: Newly diagnosed Acute Myeloid Leukemia patients who received clofarabine (1-2 hour intravenous infusion of 40mg/m2 daily dose) plus cytarabine (2-4 hours maximum intravenous infusion of 1g/m2 daily dose) starting 3-4 hours post completion of clofarabine administration on days 1 through 5, who were evaluable for response by bone marrow biopsy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day) | Complete Clinical Response | 2 participants |
Secondary
Overall Survival
Number of months of survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m\^2/Day) + Cytarabine (1g/m\^2/Day).
Time frame: Up to 24 months
Population: Results data are not available due to low/insufficient subject accrual from early \[trial\] termination.
Secondary
Predictive Factors for Response to Treatment.
Evaluation of potential factors that are predictive of clinical response in newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m\^2/Day) + Cytarabine (1g/m\^2/Day).
Time frame: Up to 1 year
Population: Results data are not available due to low/insufficient subject accrual from early \[trial\] termination.
Secondary
Relapse Free Survival
Number of months of relapse free survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m\^2/Day) + Cytarabine (1g/m\^2/Day).
Time frame: Up to 24 months
Population: Results data are not available due to low/insufficient subject accrual from early \[trial\] termination.