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

Sponsors and Collaborators:	University of Cincinnati Novartis
Information provided by:	University of Cincinnati
ClinicalTrials.gov Identifier:	NCT00594555

Purpose

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

Condition	Intervention	Phase
Chronic Myeloid Leukemia, Blast Crisis Acute Myeloid Leukemia	Drug: Imatinib Mesylate Drug: CLAG	Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine Cytarabine hydrochloride Imatinib Imatinib mesylate Granulocyte colony-stimulating factor Cladribine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study
Official Title:	A Phase II Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Acute Myeloid Leukemia

Further study details as provided by University of Cincinnati:

Primary Outcome Measures:

Establishing the overall response rate and the safety of combining imatinib mesylate with CLAG regimen [ Time Frame: The amount of time it takes to enroll 20 pts. About 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The sample size is calculated based on two stage Phase II clinical design. Ten patients will be accrued during stage 1 and 10 during stage 2). [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	November 2007
Estimated Study Completion Date:	November 2008
Estimated Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Single Arm - treatment period: Experimental Drug Name/Days Administered Neupogen/Days 1-6 CLAG/Days 2-6 Gleevec/Days 2-15	Drug: Imatinib Mesylate Imatinib Mesylate: 400mg po BID every day. Imatinib Mesylate will be administered Day 2 to Day 15 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

Arms

Assigned Interventions

Single Arm - treatment period: Experimental

Drug Name/Days Administered

Neupogen/Days 1-6

CLAG/Days 2-6

Gleevec/Days 2-15

Drug: Imatinib Mesylate

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

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594555

Locations

United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267

Sponsors and Collaborators

University of Cincinnati

Novartis

Investigators

Principal Investigator:

Rami S Komrokji, MD

The University of Cincinnati

More Information

Responsible Party:	The University of Cincinnati ( Rami Komrokji, MD )
Study ID Numbers:	CST1571AU235 / Komrokji, CST1571AUS235
Study First Received:	January 3, 2008
Last Updated:	October 29, 2008
ClinicalTrials.gov Identifier:	NCT00594555
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Cincinnati:

Blood disease, bone marrow
AML
CML,Blast Crisis

Study placed in the following topic categories:

Cladribine
Blast Crisis
Chronic myelogenous leukemia
Hematologic Diseases
Myeloproliferative Disorders
Acute myelogenous leukemia
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Imatinib
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases
Acute myelocytic leukemia
Cytarabine

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents

Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplastic Processes
Pathologic Processes
Therapeutic Uses
Cell Transformation, Neoplastic

ClinicalTrials.gov processed this record on January 16, 2009