- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00955916
CLAG Gleevec in Relapsed or Refractory Acute Myeloid Leukemia (AML)
A Phase II Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Relapsed or Refractory Acute Myeloid Leukemia
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: CLAG Regimen with Gleevec®
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
|
The CLAG regimen consisted of: Cladribine, 5 mg/m^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
Other Names:
Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15.
Re-induction was allowed if participant had partial response (PR).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: 8 weeks per participant
|
Overall Response Rate: Morphologic Complete Remission (CR) + Morphologic Complete Remission with incomplete blood count recovery (CRi) for evaluable participants.
CR - Bone Marrow: < 5% blasts without Auer rods with at least 20% cellularity with maturation of all cell lines, No presence of unique phenotype by flow cytometry identical to what was found in the pretreatment specimen, No persistent dysplasia; Peripheral: normal blood counts, absolute neutrophil count (ANC) > 1.0 k/μl and platelets > 100 k/μl ANC > 1.0 k/μl and platelets > 100 k/μl (Peripheral blood counts documenting recovery can be utilized within 4 weeks of the bone marrow); No evidence of extramedullary leukemia.
CRi - All CR criteria are met except for residual Neutropenia <1.0 x 10^9/L platelets < 100 k/μl.
|
8 weeks per participant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Progression Free Survival (PFS)
Time Frame: Up to 3 years
|
Progression Free Survival is defined as the duration of time from start of treatment to time of progression.
Leukemia related failure (progressive disease): Failure to induce bone marrow hypoplasia after 2 cycles or regrowth of leukemic blasts ≥ 20%.
|
Up to 3 years
|
Median Overall Survival (OS)
Time Frame: Up to 3 years
|
Overall Survival is defined as the time from randomization until death from any cause.
|
Up to 3 years
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia, Myeloid
- Leukemia
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Cytarabine
- Imatinib Mesylate
- Cladribine
Other Study ID Numbers
- MCC-15787
- CSTI571AUS235 (OTHER: Novartis)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Leukemia
-
Stanford UniversityTerminatedLeukemia | Leukemia, Lymphocytic, Acute | Leukemia Acute Promyelocytic Leukemia (APL) | Leukemia Acute Lymphoid Leukemia (ALL) | Leukemia Chronic Myelogenous Leukemia (CML) | Leukemia Acute Myeloid Leukemia (AML) | Leukemia Chronic Lymphocytic Leukemia (CLL)United States
-
Massachusetts General HospitalCelgene CorporationTerminatedAcute Myelogenous Leukemia | Acute Myeloid Leukemia (AML) | Acute Myelocytic Leukemia | Acute Granulocytic Leukemia | Acute Non-Lymphocytic LeukemiaUnited States
-
Institute of Hematology & Blood Diseases HospitalBejing Institute for Stem Cell and Regenerative Medicine; Institute for Stem...RecruitingRefractory Leukemia | Relapsed Leukemia | Acute Myeloid Leukemia, ChildhoodChina
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States
-
Hybrigenics CorporationUnknownAcute Myelogenous LeukemiaUnited States, France
-
Betta Pharmaceuticals Co., Ltd.Not yet recruitingAcute Myeloid Leukemia LeukemiaChina
-
Beijing Boren HospitalRecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapse LeukemiaChina
-
Center for International Blood and Marrow Transplant...National Marrow Donor Program; St. Baldrick's FoundationActive, not recruitingAcute Myelogenous LeukemiaUnited States
-
Massachusetts General HospitalCompleted
-
Kinex Pharmaceuticals Inc.CompletedAcute Myelogenous LeukemiaUnited States
Clinical Trials on CLAG Regimen
-
Nanfang Hospital, Southern Medical UniversityNot yet recruiting
-
Zhejiang UniversityFirst People's Hospital of Hangzhou; Second Affiliated Hospital, School of... and other collaboratorsRecruiting
-
University of Michigan Rogel Cancer CenterGenentech, Inc.Not yet recruitingSecondary Acute Myeloid LeukemiaUnited States
-
Medical University of South CarolinaTerminatedHematological MalignanciesUnited States
-
Pearl Therapeutics, Inc.CompletedChronic Obstructive Pulmonary DiseaseUnited States
-
GlaxoSmithKlineCompleted
-
University of BedfordshireUnknownCardiovascular Diseases | Diabetes | Sedentary Lifestyle | Type 2 Diabetes | Sedentary Behavior | Cardiovascular Risk FactorUnited Kingdom
-
Chinese PLA General HospitalThe General Hospital of Western Theater Command; First Hospital of China Medical... and other collaboratorsRecruitingRelapsed/Refractory Acute Myeloid LeukemiaChina
-
University of CincinnatiNovartisWithdrawnA Study Evaluating the Effects of CLAG With Gleevec in Refractory or Relapsed Acute Myeloid LeukemiaAcute Myeloid Leukemia | Chronic Myeloid Leukemia, Blast CrisisUnited States
-
Florida State UniversityAlliance for Potato Research and EducationCompletedOverweight and Obesity | Type2 Diabetes | Arterial Stiffness | Cardiometabolic SyndromeUnited States