Clinical trial NCT00814164: Clofarabine and Daunorubicin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Keywords: adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
untreated adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary acute myeloid leukemia
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2008-12-24
Enrollment: 21
Sex: ALL
Minimum age (years): 60
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete Remission (CR)
timeFrame: 2 years
Secondary outcomes:
measure: Disease-free Survival
timeFrame: 5 years
measure: Overall Survival
timeFrame: 4 years
measure: Differences in Disease-free and Overall Survival Between Patients Whose Cells do or do Not Demonstrate Apoptosis Following Clofarabine and Daunorubicin Hydrochloride Therapy
timeFrame: 4 years
measure: Difference in Disease-free and Overall Survival According to p53R2 Protein Sizes
timeFrame: 4 years
measure: Difference in Disease-free and Overall Survival According to Multi-drug Resistance Protein Expression
timeFrame: 4 years
measure: Difference in Disease-free and Overall Survival Based on Clofarabine Triphosphate Levels
timeFrame: 4 years
measure: A Preliminary Relationship Between Treatment Outcome and Biologic Parameters
timeFrame: 4 years
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Meir Wetzler, MD
role: PRINCIPAL_INVESTIGATOR
References: