Clinical trial NCT01960387: Phase II Clofarabine and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
clofarabine
cytarabine
persistent AML
induction therapy
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2013-10-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Complete Clinical Response
timeFrame: Between 14 and 28 days from start of study treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 24 months
measure: Relapse Free Survival
timeFrame: Up to 24 months
measure: Predictive Factors for Response to Treatment.
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Michael Boyiadzis, M.D., M.H.Sc
role: PRINCIPAL_INVESTIGATOR
References: