Phase II Clofarabine and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study of Clofarabine and Cytarabine for Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Persistent Disease After Treatment With an Anthracycline and Cytarabine

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Clofarabine
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Able to understand and have the ability to provide written informed consent Patients over 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Left ventricular ejection fraction (LVEF) ≥ 50% Negative urine pregnancy test for all females All subjects must agree to use an effective method of contraception while receiving the study drugs Exclusion Criteria: Diagnosis of acute promyelocytic leukemia Relapsed AML Prior use of clofarabine Previous allogeneic or autologous hematopoietic cell transplantation Impaired liver function (serum total bilirubin > 2.0 mg/dL, alanine aminotransferase and aspartate aminotransferase ≥ 4 x the upper limit of normal) Impaired renal function (serum creatinine ≥ 2.0 mg/dL) Uncontrolled or life-threatening infection that is not responding to antimicrobial therapy History of a psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent 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 Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory or cardiac disease)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clofarabine and Cytarabine<br>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. Cytarabine at a dose of 1g/m2 daily will then be given as a 2-hour intravenous infusion, starting 3 hours after the completion of clofarabine administration on days 1 through 5. | Drug: Clofarabine<br>* 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.<br>* Other names: Purine nucleoside analog;Drug: Cytarabine<br>* 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.<br>* Other names: Pyrimidine analog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Between 14 and 28 days from start of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Up to 24 months | 
| 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). | Up to 24 months | 
| 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). | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, clofarabine, cytarabine, persistent AML, induction therapy