Study of Imatinib-Combined Chemotherapy for BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) - Full Text View

Sponsored by:	Japan Adult Leukemia Study Group
Information provided by:	Japan Adult Leukemia Study Group
ClinicalTrials.gov Identifier:	NCT00130195

Purpose

The purpose of this study is to determine the clinical efficacy and safety of imatinib-combined chemotherapy on newly diagnosed BCR-ABL-positive ALL.

Condition	Intervention	Phase
Acute Lymphoblastic Leukemia	Drug: imatinib Drug: cyclophosphamide Drug: daunorubicin Drug: vincristine Drug: prednisolone Drug: methotrexate Drug: cytarabine Drug: dexamethasone	Phase II

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

Drug Information available for: Cyclophosphamide Cytarabine Cytarabine hydrochloride Daunorubicin hydrochloride Daunorubicin Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Methotrexate Prednisolone 6-Methylprednisolone Depo-medrol Medrol veriderm Methylprednisolone Methylprednisolone hemisuccinate Methylprednisolone Sodium Succinate Prednisolone acetate Prednisolone sodium phosphate Prednisolone Sodium Succinate Vincristine sulfate Vincristine Imatinib Imatinib mesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Efficacy Study
Official Title:	Phase 2 Study of Imatinib-Combined Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia

Further study details as provided by Japan Adult Leukemia Study Group:

Primary Outcome Measures:

The rate of complete remission [ Time Frame: 63 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The duration of remission [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Toxicity caused by combination of imatinib and chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment:	100
Study Start Date:	September 2002
Study Completion Date:	May 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Drug: imatinib Drug: cyclophosphamide Drug: daunorubicin Drug: vincristine Drug: prednisolone Drug: methotrexate Drug: cytarabine Drug: dexamethasone

Detailed Description:

Philadelphia chromosome (Ph) is a translocation abnormality leading to the formation of the BCR-ABL gene rearrangement. This genetic abnormality occurs in up to 30% of adult acute lymphoblastic leukemia (ALL), and its presence is known to be the most adverse prognostic factor for ALL. Because long-term survival cannot be achieved by conventional chemotherapy alone, there is a clear medical need for alternative treatment approaches. Imatinib is a potent selective inhibitor of the BCR-ABL protein kinase, and it has been reported that single-agent imatinib induced response in a substantial proportion of Ph-positive ALL (Ph+ALL) patients, but that the response was not durable. The Japan Adult Leukemia Study Group (JALSG) has therefore started a phase 2 study designed to evaluate the clinical effect of imatinib-combined chemotherapy on newly diagnosed BCR-ABL-positive ALL.

Eligibility

Ages Eligible for Study:	15 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Previously untreated BCR-ABL-positive ALL
Age between 15 and 64 years
Performance status between 0 and 3 (ECOG criteria)
Adequate functioning of the liver (serum bilirubin level < 2.0 mg/dL), kidneys (serum creatinine level < 2.0 mg/dL), and heart (left ventricular ejection fraction greater than 50% and no severe abnormalities detected on electrocardiograms and echocardiographs)
Written informed consent to participate in the trial

Exclusion Criteria:

Uncontrolled active infection
Another severe and/or life-threatening disease
Positive for HIV antibody and/or hepatitis B surface (HBs) antigen tests
Another primary malignancy which is clinically active and/or requires medical interventions
Pregnant and/or lactating women
Past history of renal failure

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00130195

Locations

Japan
Department of Hematology, Nagoya University Graduate School of Medicine
Nagoya, Japan, 466-8550

Sponsors and Collaborators

Japan Adult Leukemia Study Group

Investigators

Study Director:	Fumihiko Hayakawa, MD	Nagoya University Graduate School of Medicine
Study Chair:	Tomoki Naoe, MD	Nagoya University Graduate School of Medicine

More Information

The JALSG homepage This link exits the ClinicalTrials.gov site

Publications of Results:

Towatari M, Yanada M, Usui N, Takeuchi J, Sugiura I, Takeuchi M, Yagasaki F, Kawai Y, Miyawaki S, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R; Japan Adult Leukemia Study Group. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood. 2004 Dec 1;104(12):3507-12. Epub 2004 Aug 17.

Yanada M, Takeuchi J, Sugiura I, Akiyama H, Usui N, Yagasaki F, Kobayashi T, Ueda Y, Takeuchi M, Miyawaki S, Maruta A, Emi N, Miyazaki Y, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R; Japan Adult Leukemia Study Group. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006 Jan 20;24(3):460-6. Epub 2005 Dec 12.

Yanada M, Takeuchi J, Sugiura I, Akiyama H, Usui N, Yagasaki F, Nishii K, Ueda Y, Takeuchi M, Miyawaki S, Maruta A, Narimatsu H, Miyazaki Y, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R; Japan Adult Leukemia Study Group. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. Haematologica. 2008 Feb;93(2):287-90. Epub 2008 Jan 26.

Study ID Numbers:	JALSG Ph+ALL202
Study First Received:	August 12, 2005
Last Updated:	November 13, 2008
ClinicalTrials.gov Identifier:	NCT00130195
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Japan Adult Leukemia Study Group:

acute lymphoblastic leukemia
BCR-ABL
Philadelphia-chromosome
newly diagnosed

Study placed in the following topic categories:

Dexamethasone
Philadelphia Chromosome
Daunorubicin
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Methylprednisolone
Vincristine
Methylprednisolone acetate
Prednisolone acetate
Cyclophosphamide

Folic Acid
Imatinib
Leukemia
Lymphatic Diseases
Prednisolone
Methotrexate
Lymphoproliferative Disorders
Lymphoma
Cytarabine
Dexamethasone acetate
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Reproductive Control Agents
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Hormones
Therapeutic Uses

Abortifacient Agents
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Mitosis Modulators
Gastrointestinal Agents
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Antiviral Agents

ClinicalTrials.gov processed this record on January 16, 2009