Clofarabine and Daunorubicin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

A Phase II Study Evaluating Mechanisms of Resistance Following Treatment With Clofarabine and Daunorubicin in Newly Diagnosed Adult Acute Myeloid Leukemia Patients > or = to 60 Years Old

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00814164
• Other study ID #: CDR0000630678
• Secondary ID: RPCI-I-132208
• Status: Terminated
• Phase: Phase 2
• First received: December 23, 2008
• Last updated: August 13, 2013
• Start date: December 2008
• Est. completion date: August 2013

Study information

• Verified date: August 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as clofarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving clofarabine together with daunorubicin may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving clofarabine together with daunorubicin works in treating older patients with newly diagnosed acute myeloid leukemia.

Description:

OBJECTIVES:

Primary

• Study complete response (CR) and CR without platelet recovery (CRp) following treatment with clofarabine and daunorubicin hydrochloride in older patients with newly diagnosed acute myeloid leukemia.

Secondary

• Study disease-free and overall survival of these patients following treatment with this regimen.

• Compare disease-free and overall survival of patients whose cells do or do not demonstrate apoptosis following treatment with this regimen.

OUTLINE:

• Induction therapy: Patients receive clofarabine IV over 1 hour on days 1-5 and daunorubicin hydrochloride IV over 5 minutes on days 1, 3, and 5. Patients are assessed after induction course 1. Patients with ≥ 5% blasts in bone marrow may receive another course of induction therapy beginning between 28-84 days after initiation of course 1. Patients who achieve complete remission (CR) or CR without platelet recovery (CRp) (after 1 or 2 courses of induction therapy) proceed to consolidation therapy.

• Consolidation therapy: Beginning between 28 -84 days after initiation of last course of induction therapy, patients receive clofarabine IV over 1 hour on days 1-3 and daunorubicin hydrochloride IV over 5 minutes on days 1 and 3. Patients may receive a second course of consolidation therapy beginning between 28-84 days of consolidation course 1.

Blood and bone marrow samples are collected periodically to assess response and for pharmacokinetic, cytogenetic, immunophenotyping, and molecular analyses.

After completion of study treatment, patients are followed for at least 2 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: August 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Newly diagnosed acute myeloid leukemia

• At least 10% blasts in the peripheral blood

• De novo or secondary disease

• No acute promyelocytic leukemia with t[15;17] or any other variant

• No clinical evidence of CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Serum bilirubin = 1.5 times upper limit of normal (ULN)

• AST and ALT = 2.5 times ULN

• Alkaline phosphatase = 2.5 times ULN

• LVEF = 45%

• Estimated glomerular filtration rate = 50 mL/min

• Not pregnant or nursing

• Fertile patients must use effective barrier contraception during and for at least 6 months following study treatment

• No known HIV positivity

• Able to comply with study procedures and follow-up examinations

• No psychiatric disorders that would interfere with consent, study participation, or follow-up

• No uncontrolled systemic fungal, bacterial, viral, or other infection (i.e., exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)

• No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo induction therapy with both agents

• No other malignancy, unless disease-free for at least 3 years following curative intent therapy

• Nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are allowed if definitive treatment for the condition has been completed

• Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed

• No other severe concurrent disease

PRIOR CONCURRENT THERAPY:

• No other concurrent systemic antileukemic therapy (standard or investigational)

• No concurrent cytotoxic therapy or investigational therapy

• No concurrent alternative medications (e.g., herbal or botanical for anticancer purposes)

• No prior chemotherapy

• Prior hydroxyurea allowed

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• clofarabine
IV
• daunorubicin hydrochloride
IV

Genetic:
• cytogenetic analysis
Correlative study
• protein expression analysis
Correlative Study

Other:
• immunologic technique
Correlative Study
• pharmacological study
Correlative Study

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission (CR) or complete remission in the absence of total platelet recovery (CRp)		2 years	No
Secondary	Disease-free survival		5 years	No
Secondary	Overall survival		4 years	No
Secondary	Differences in disease-free and overall survival between patients whose cells do or do not demonstrate apoptosis following clofarabine and daunorubicin hydrochloride therapy		4 years	No
Secondary	Difference in disease-free and overall survival according to p53R2 protein sizes		4 years	No
Secondary	Difference in disease-free and overall survival according to multi-drug resistance protein expression		4 years	No
Secondary	Difference in disease-free and overall survival based on clofarabine triphosphate levels		4 years	No
Secondary	A preliminary relationship between treatment outcome and biologic parameters		4 years	No