ESHAP-Imatinib for Refractory/Relapsed Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Open-labeled, multicenter, phase I/II study of imatinib combined with ESHAP as salvage therapy in relapsed/refractory non-Hodgkin's lymphoma

Official Title
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Open-labeled, Multicenter, Phase I/II Study of Imatinib Combined With ESHAP as Salvage Therapy in Relapsed/Refractory Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: ESHAP-Imatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically diagnosed non-Hodgkin's lymphoma, refractory or relapsed after 1st line treatment. Paraffin block of the lesions available for immunohistochemical analysis Candidate for ESHAP salvage therapy Evidence of at least one lesion with a diameter of 1.5 cm Age of over 20 years Eastern cooperative oncology group performance status (ECOG) less than or equal to 2. Adequate kidney function with serum creatinine< 2.5 mg/dL, creatinine clearance ≥ 50 mL/min Adequate liver function with aspartate transaminase (AST)/alanine aminotransferase (ALT) lower than or equal to 3 times the normal upper limit; Total bilirubin lower than or equal to 1.5 times the upper limit ;alkaline phosphatase lower than or equal to 5 times the normal upper limit. Adequate bone marrow function with absolute neutrophil count ≥ 1,000/uL; platelets ≥ 75,000/uL; hemoglobin ≥ 9.0 g/dL Patients who gave voluntarily informed consent before performing any test test that is not part of routine care of patients Exclusion Criteria: Patients with history of exposure to imatinib or other Bcr-Abl tyrosine-kinase inhibitors Known or suspected hypersensitivity to imatinib Potential use or usage alteration of CYP3A4 inducers or inhibitors from prior to 21 days of to the test regimen until the initiation of round 2 ESHAP. Exceptions are itraconazole and fluconazole for treatment or prevention of fungal infection, hydrocortisone and dexamethasone for treatment of nausea/vomiting/fluid retention, and methylprednisolone as a part of the ESHAP regimen. Known involvement of the central nervous system (CNS) by lymphoma. Pregnant or breast-feeding. Females of childbearing potential who do not agree to undergo pregnancy tests or repeated use effective birth control while included in the clinical trial. Serious or uncontrolled medical condition, such as presence of abnormal or clinically significant cardiac disease, such as acute myocardial infarction or unstable angina within 6 months prior to initiation of treatment with ESHAP-imatinib, serious neurological or psychological conditions such as dementia or epilepsy, or uncontrolled active infection. Prior history of malignancy other than to non-Hodgkin's lymphoma (except basal or squamous cell skin and in situ carcinoma of the cervix) unless the patient free of disease beyond 5 years are. HIV positive and in treatment.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESHAP-Imatinib 100mg<br>Imatinib 100 mg combined with ESHAP * ESAHP D1-4 Etoposide 40mg/m2 D1-4 Cisplatin 25mg/m2 D5 Cytarabine 2000mg/m2 D1-5 Methylprednisolone 250mg/m2 D6 Pegfilgrastim 6mg | Drug: ESHAP-Imatinib<br>* After selection of the maximum-tolerated dose of the combination ESHAP with imatinib a phase 2 of the study will be performed in order to evaluate the ORR of ESHAP-imatinib.<br>|
| Experimental: ESHAP-Imatinib 200mg<br>Imatinib 200 mg combined with ESHAP * ESAHP D1-4 Etoposide 40mg/m2 D1-4 Cisplatin 25mg/m2 D5 Cytarabine 2000mg/m2 D1-5 Methylprednisolone 250mg/m2 D6 Pegfilgrastim 6mg | Drug: ESHAP-Imatinib<br>* After selection of the maximum-tolerated dose of the combination ESHAP with imatinib a phase 2 of the study will be performed in order to evaluate the ORR of ESHAP-imatinib.<br>|
| Experimental: ESHAP-Imatinib 400mg<br>Imatinib 400 mg combined with ESHAP * ESAHP D1-4 Etoposide 40mg/m2 D1-4 Cisplatin 25mg/m2 D5 Cytarabine 2000mg/m2 D1-5 Methylprednisolone 250mg/m2 D6 Pegfilgrastim 6mg | Drug: ESHAP-Imatinib<br>* After selection of the maximum-tolerated dose of the combination ESHAP with imatinib a phase 2 of the study will be performed in order to evaluate the ORR of ESHAP-imatinib.<br>|
| Experimental: ESHAP-Imatinib 300mg<br>Imatinib 300 mg combined with ESHAP * ESAHP D1-4 Etoposide 40mg/m2 D1-4 Cisplatin 25mg/m2 D5 Cytarabine 2000mg/m2 D1-5 Methylprednisolone 250mg/m2 D6 Pegfilgrastim 6mg | Drug: ESHAP-Imatinib<br>* After selection of the maximum-tolerated dose of the combination ESHAP with imatinib a phase 2 of the study will be performed in order to evaluate the ORR of ESHAP-imatinib.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Adverse events are recorded and analyzed from the time of enrollment to last day of ESHAP-imatinib treatment | Up to 33 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I/II Overall Response Rate (ORR) |  | Week 4, Week 10, Week 16 | 
| Phase II Event-Free Survival |  | Up to 3 years | 
| Phase II Overall Survival |  | Up to 3 years |