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

Tracking Information
First Submitted Date ICMJE	April 17, 2009
First Posted Date ICMJE	April 20, 2009
Results First Submitted Date	January 29, 2018
Results First Posted Date	March 29, 2018
Last Update Posted Date	April 25, 2018
Study Start Date ICMJE	December 2004
Actual Primary Completion Date	June 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 1, 2018)	Objective Response Rate [ Time Frame: 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 ]; 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).
Original Primary Outcome Measures ICMJE; (submitted: April 17, 2009)	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. [ Time Frame: 1 year ]
Change History	Complete list of historical versions of study NCT00884286 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 1, 2018)	Time to Response Onset [ Time Frame: 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 response onset was defined as the time from the first day of plitidepsin treatment to the first documentation of response.; Duration of Response [ Time Frame: 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 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.; Time to Progression [ Time Frame: 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 (TTP) was to be calculated from the first day of plitidepsin treatment to the date of disease progression.; Time to Subsequent Chemotherapy [ Time Frame: 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 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.; Progression-free Survival [ Time Frame: 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 (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.; Overall Survival [ Time Frame: 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 (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.
Original Secondary Outcome Measures ICMJE; (submitted: April 17, 2009)	To investigate the safety profile of Aplidin® in the patient population and to obtain additional pharmacokinetic information for the drug [ Time Frame: 1 year ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Multicenter Trial to Treat Patients With Relapsed/Refractory Aggressive Non Hodgkin Lymphoma
Official Title ICMJE	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
Brief Summary	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	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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Leukemia; Lymphoma
Intervention ICMJE	Drug: Aplidin®; 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.; Other Name: plitidepsin
Study Arms	Experimental: Arm One; Aplidin® given as a 1-hour weekly IV infusion; Intervention: Drug: Aplidin®
Publications *	Ribrag V, Caballero D, Fermé C, Zucca E, Arranz R, Briones J, Gisselbrecht C, Salles G, Gianni AM, Gomez H, Kahatt C, Corrado C, Szyldergemajn S, Extremera S, de Miguel B, Cullell-Young M, Cavalli F. Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin's lymphoma. Haematologica. 2013 Mar;98(3):357-63. doi: 10.3324/haematol.2012.069757. Epub 2012 Oct 12.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 10, 2011)	67
Original Estimated Enrollment ICMJE; (submitted: April 17, 2009)	58
Actual Study Completion Date	June 2010
Actual Primary Completion Date	June 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	France, Italy, Peru, Puerto Rico, Spain, Switzerland
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00884286
Other Study ID Numbers ICMJE	APL-B-013-02
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: No
Responsible Party	PharmaMar
Study Sponsor ICMJE	PharmaMar
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Vincent Ribrag, MD Institut Gustave Roussy, France
PRS Account	PharmaMar
Verification Date	February 2011
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP