Clinical trial NCT00955916: CLAG Gleevec in Relapsed or Refractory Acute Myeloid Leukemia (AML)
Official title: A Phase II Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: relapsed
refractory
acute
myeloid
AML
CML
blast crisis
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2009-08-10
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to find out what effects (good and bad) Gleevec® (Imatinib mesylate) combined with chemotherapy has on participants and their acute myeloid leukemia.

Detailed description: In relapsed or resistant acute myeloid leukemia (a type of blood cancer where immature blood cells are increased, blocking normal blood cell production), different types of chemotherapy are used for treatment. Patients responded to all the chemotherapies in similar ways, but most of the responses did not last long if further stem cell transplantation was not done. Gleevec is believed to work by interfering with the abnormal protein by blocking it from telling the body to keep making more white blood cells that are abnormal.

The CLAG regimen is the standard chemotherapy used for relapsed AML (Acute Myeloid Leukemia). This study will add Gleevec® to the regimen for a period of 14 days. Gleevec® is approved by the Food and Drug Administration (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.

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 World Health Organization (WHO) criteria, except acute promyelocytic leukemia AML-M3 French-American-British (FAB) subgroup. A documentation of relapse is required by a bone marrow/aspirate within 4 weeks of registration.
* 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 complete response (CR) (more than 5% myeloblasts). Early relapse is defined as that occurring within 12 months and late relapse is defines as that occurring after 12 months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Patients must sign a written informed consent.
* Females of childbearing potential (FOCP) 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.
* Prior allogeneic or autologous stem cell transplantation is allowed.

Exclusion Criteria:

* Abnormal Kidney Functions: creatinine ≥2.5 mg/dL.
* Abnormal Liver Functions: Bilirubin more 3 mg/dL, transaminases (AST/ALT) more than 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 (NYHA) Criteria ( i.e., congestive heart failure, myocardial infarction within 6 months of the study), or ejection fraction (EF)\< 30%.
* Patient has known chronic liver disease (i.e., chronic active hepatitis, hepatitis B, hepatitis C, and cirrhosis).
* Patient has known diagnosis of human immunodeficiency virus (HIV) infection.
* History of other malignancy, except non-melanotic skin cancers or no disease recurrence/progression for more than 2 years.
* 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
* Prior therapy with CLAG chemotherapy regimen
* Any adverse event attributable to previous chemotherapy regimen must be resolved to grade 1 or less at time of registration.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 8 weeks per participant
Secondary outcomes:
measure: Median Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Median Overall Survival (OS)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Rami Komrokji, M.D.
role: PRINCIPAL_INVESTIGATOR
References: