Clinical trial NCT00130195: Study of Imatinib-Combined Chemotherapy for BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL)
Official title: Phase 2 Study of Imatinib-Combined Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: acute lymphoblastic leukemia
BCR-ABL
Philadelphia-chromosome
newly diagnosed
Lead sponsor: Japan Adult Leukemia Study Group
Sponsor class: OTHER
First posted: 2005-08-15
Enrollment: 100
Sex: ALL
Minimum age (years): 15
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: The rate of complete remission
timeFrame: 63 days
Secondary outcomes:
measure: The duration of remission
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: Toxicity caused by combination of imatinib and chemotherapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Department of Hematology, Nagoya University Graduate School of Medicine
Study officials:
affiliation: Nagoya University
name: Fumihiko Hayakawa, MD
role: STUDY_DIRECTOR
affiliation: Nagoya University
name: Tomoki Naoe, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1182/blood-2004-04-1389. Epub 2004 Aug 17.
citation: 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. doi: 10.1200/JCO.2005.03.2177. Epub 2005 Dec 12.
citation: 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. doi: 10.3324/haematol.11891. Epub 2008 Jan 26.