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

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

ChemIDplus related topics:

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: After remission induction therapy ]

Secondary Outcome Measures:

The duration of remission [ Time Frame: During the follow-up period ]
Overall survival [ Time Frame: 1 year ]
Toxicity caused by combination of imatinib and chemotherapy [ Time Frame: During the follow-up period ]

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 65 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:	Masamitsu Yanada, 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
First Received:	August 12, 2005
Last Updated:	July 3, 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 October 03, 2008

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