Multicenter Trial to Treat Patients With Relapsed/Refractory Aggressive Non Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is a multicenter study to assess the anti-tumour activity,to investigate the safety profile and to obtain additional pharmacokinetic information for Aplidin® given as 1-hour weekly IV infusion in patients with aggressive non-Hodgkin's Lymphoma.

Detailed Description
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A Phase II Multicenter,Open-Label, Clinical And Pharmacokinetic Study Of Aplidin® As A 1-Hour Weekly IV Infusion, In Patients With Relapsed Or Refractory aggressive non-Hodgkin's Lymphoma. Primary • To assess the anti-tumour activity of Aplidin® given as a 1-hour weekly IV infusion, in patients with aggressive non-Hodgkin's Lymphoma, relapsing or refractory to a prior therapy. Secondary To further investigate the safety profile of Aplidin® given as 1-hour weekly IV infusion in this patient population. To obtain additional pharmacokinetic information for Aplidin® given as 1-hour weekly IV infusion in patients with aggressive non-Hodgkin's Lymphoma.

Official Title
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A Phase II Multicenter, Open-Label, Clinical And Pharmacokinetic Study of Aplidin® As A 1-Hour Weekly IV Infusion, in Patients With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: Aplidin®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Histologically confirmed aggressive lymphomas, Patient requires treatment because NHL relapses Measurable disease Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed. Age > 18 years. Performance status (ECOG) < 2 Adequate renal, hepatic, and bone marrow function (assessed < 14 days before inclusion in the study) Left ventricular ejection fraction within normal limits. Exclusion Criteria: Prior therapy with Aplidin®. Concomitant therapy with any anti-lymphoproliferative agent Acute lymphoblastic leukemia. CNS lymphoma. HIV-associated lymphoma. Prior gene therapy with viral vectors. More than three previous lines of systemic biological agents or chemotherapies. Wash-out periods since the end of the precedent therapy less than: 6 weeks for nitroso-urea or high dose chemotherapy 3 weeks for other chemotherapies or biological agents 4 weeks for radiation or radionuclide therapy (6 weeks in case of prior extensive external beam radiation (more than 25% of bone marrow distribution). 4 weeks for major prior surgery 30 days for any investigational product 4 weeks for immunosuppressive therapy after allogeneic hematopoietic stem cell transplantation. Pregnant or lactating women. Men and women of reproductive potential who are not using effective contraceptive methods History of another neoplastic disease. Exceptions: Non-melanoma skin cancer,cCarcinoma in situ of any site,any other cancer curatively treated and no evidence of disease for at least 10 years. Known cerebral or leptomeningeal involvement. Other relevant diseases or adverse clinical conditions Treatment with any investigational product in the 30 days period before inclusion in the study. Known hypersensitivity to Aplidin®, mannitol, cremophor EL, or ethanol Limitation of the patient's ability to comply with the treatment or follow-up protocol.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm One<br>Aplidin® given as a 1-hour weekly IV infusion | Drug: Aplidin®<br>* Aplidin® will be administered at a starting dose of 3.2 mg/m2, as a 1-hour intravenous infusion, on days 1, 8 and 15, every 28 days cycle.<br>* Other names: plitidepsin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The primary objective of the study was the exploration of the efficacy of plitidepsin when given as a weekly 1-hour infusion on Days 1, 8 and 15 in 4-week cycles to patients with relapsed or refractory aggressive non-Hodgkin's Lymphoma. The primary efficacy endpoint was the Objective Response Rate, defined as the combined rate of Complete Response (CR), Unconfirmed Complete Response (CRu) and Partial Response (PR) following the definition of response according to the International Working Group (IWG) criteria for Non-Hodgkin's Lymphoma (NHL). | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Response Onset | Time to response onset was defined as the time from the first day of plitidepsin treatment to the first documentation of response. | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 
| Duration of Response | Duration of response was defined as the time from the first documented objective response (CR, CRu or PR) to disease progression or death. Patients who had not progressed or died were to have their duration censored at the date of their last disease assessment. | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 
| Time to Progression | Time to progression (TTP) was to be calculated from the first day of plitidepsin treatment to the date of disease progression. | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 
| Time to Subsequent Chemotherapy | Time to subsequent therapy was to be calculated from the first infusion of the study drug to the start date of the subsequent therapy. Patients without subsequent therapy were to be censored at their last reported date. | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 
| Progression-free Survival | Progression-free survival (PFS) was to be calculated from the date of registration to the date of first objective disease progression or death from any cause. Patients who were lost to follow-up without documentation of progression were to be censored at the last date they were assessed and found progression-free. A patient receiving a new treatment in the absence of documented progression was to be considered as progressing at the time of re-treatment. | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 
| Overall Survival | Overall survival (OS) was to be calculated from the date of registration to the date of death from any cause. Patients with no documented death were to be censored at the last date they were known to be alive. | All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aplidin, Aggressive Non Hodgkin Lymphoma, Leukemia-Lymphoma, Adult T-Cell and B-cell