A Study Evaluating the Effects of CLAG With Gleevec in Refractory or Relapsed Acute Myeloid Leukemia

NCT ID: NCT00594555

Last Updated: 2008-10-31

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2008-11-30

Brief Summary

The purpose of this study is to evaluate the safety of combined chemotherapy treatment (CLAG regimen) with Imatinib Mesylate (Gleevec) in patients with AML.

Detailed Description

In relapsed or resistant acute myeloid leukemia (type of blood cancer where immature blood cells are increased, blocking normal blood cells production) no standard therapy exits. Response rates are similar for different chemotherapy treatments. Allogenic stem cell transplant remains the only curative option

The purpose of this study is to evaluate the safety of combined chemotherapy treatment (CLAG regimen) with Imatinib Mesylate (Gleevec). The CLAG regimen is a combination of the chemotherapy drugs cladribine and cytarabine, as well as, neupogen which increases the white blood counts.

Imatinib Mesylate is believed to work by interfering with the abnormal protein by blocking it from telling the body to keep making more and more abnormal white blood cells. Imatinib Mesylate is approved by the FDA for the treatment of chronic myeloid leukemia (CML) and some types of acute lymphoblastic leukemia (ALL). Its use in combination with CLAG regimen is considered experimental for the treatment of Acute Myeloid Leukemia / CML blast crisis

The goal of the study is to find out what effects (good and bad) Imatinib Mesylate (Gleevec)combined with chemotherapy (CLAG regimen) on acute myeloid leukemia.

Conditions

Chronic Myeloid Leukemia, Blast Crisis; Acute Myeloid Leukemia

Keywords

Blood disease, bone marrow; AML; CML,Blast Crisis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm - treatment period

Drug Name/Days Administered

Neupogen/Days 1-6

CLAG/Days 2-6

Gleevec/Days 2-15

Group Type: EXPERIMENTAL

Imatinib Mesylate

Intervention Type: DRUG

Imatinib Mesylate: 400mg po BID every day. Imatinib Mesylate will be administered Day 2 to Day 15

CLAG

Intervention Type: DRUG

Cladribine: 5mg/m2 administered through a 2 hour intravenous infusion daily for 5 consecutive days starting on Day 2

Cytarabine: 2gm/m2 administered through a 4 hour intravenous infusion starting 2 hours after the ignition of Cladribine for 5 days starting on Day 2

G-CSF: 300mcg sc for 6 days starting at 24 hours (Day 1) before the first dose of Cladribine; administration starting on Day 1 for 6 days

Interventions

Imatinib Mesylate

Imatinib Mesylate: 400mg po BID every day. Imatinib Mesylate will be administered Day 2 to Day 15

Intervention Type: DRUG

CLAG

Cladribine: 5mg/m2 administered through a 2 hour intravenous infusion daily for 5 consecutive days starting on Day 2

Cytarabine: 2gm/m2 administered through a 4 hour intravenous infusion starting 2 hours after the ignition of Cladribine for 5 days starting on Day 2

G-CSF: 300mcg sc for 6 days starting at 24 hours (Day 1) before the first dose of Cladribine; administration starting on Day 1 for 6 days

Intervention Type: DRUG

Other Intervention Names

Gleevec (Imatinib Mesylate); Cladribine, Cytarabine & G-CSF (also know as CLAG)

Eligibility Criteria

Inclusion Criteria

• Men and Women of all ethnic groups whose age is ≥ 18 years old.
• Diagnosis of AML or CML blast crisis, according to WHO criteria, except acute promyelocytic leukemia AML-M3 FAB subgroup.
• Refractory or Relapsed AML.

• Refractory AML is defined as failure to achieve CR after 2 cycles of induction chemotherapy or persistent (>40%) bone marrow blasts after one cycle of chemotherapy induction.
• Relapsed AML is defined as any evidence of disease recurrence after achieving CR. Early relapse is defined as that occurring within 12 months and late relapse is defines as that occurring after 12 months.
• ECOG performance status of 0 or 1.
• Patients must sign a written informed consent.
• Females of childbearing potential must not be pregnant or actively nursing a child. They must have a negative pregnancy test 7 days before initiation of study drug administration.
• Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Male and females of reproductive potential must agree to employ an effective barrier method of birth control throughout the duration of the trial and for 3 months following study medication discontinuation.

Exclusion Criteria

• Abnormal Kidney Functions: creatinine ≥2.5mg/dL; if creatinine is between 2.0-2.5, patient should have GFR measured and the dose of Cytarabine may be adjusted accordingly.
• Abnormal Liver Functions: Bilirubin .2mg/dL, transaminases (AST/ALT) more that 2.5 times the institutional upper limits of normal (IULN)
• Systemic active infection, unless controlled on active therapy.
• Patients with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria ( i.e., congestive heart failure, myocardial infarction within 6 months of the study), EF 30%.
• Patient has known chronic liver disease (i.e., chronic active hepatitis and cirrhosis).
• Patient has known diagnosis of human immunodeficiency virus (HIV) infection.
• History of other curatively untreated malignancy, except non-melanotic skin cancers.
• Patients that have received investigational agents within 1 month of study entry.
• History of allergic reaction attributed to compounds of similar chemical or biologic composition to Gleevec or any component of the CLAG regimen.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

The University of Cincinnati

Principal Investigators

Rami S Komrokji, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Cincinnati

Locations

University of Cincinnati

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

CST1571AUS235

Identifier Type: -

Identifier Source: secondary_id

CST1571AU235 / Komrokji

Identifier Type: -

Identifier Source: org_study_id