Phase II Clofarabine and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

— UPCI 13-066  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01960387
• Other study ID #: UPCI 13-066
• Status: Terminated
• Phase: Phase 2
• First received: October 7, 2013
• Last updated: January 14, 2016
• Start date: October 2013
• Est. completion date: March 2015

Study information

• Verified date: January 2016
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Clofarabine
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
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.

Locations

Country	Name	City	State
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	complete response	To evaluate the efficacy of clofarabine and cytarabine as second course therapy for patients with newly diagnosed acute myeloid leukemia who have persistent disease after treatment with an anthracycline and cytarabine.	1 year	No
Secondary	Number of participants with adverse events	Treatment-related toxicities will be assessed in patients who are treated with the combination of clofarabine and cytarabine.	1 year	Yes
Secondary	Length of survival	Length of survival will be assessed in patients who are treated with the combination of clofarabine and cytarabine.	1 year	No
Secondary	Relapse free survival	Relapse free survival will be assessed in patients who are treated with the combination of clofarabine and cytarabine	1 year	No
Secondary	Predictive factors for response to treatment	Stepwise logistic and proportional hazards (Cox) regression will be used to assess demographic baseline clinical variables and baseline cytogenetic information (favorable, intermediate, or adverse cytogenetics) that are predictive of CR, survival, or progression-free survival.	1 year	No