Clinical trial NCT00884286: Multicenter Trial to Treat Patients With Relapsed/Refractory Aggressive Non Hodgkin Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: Aplidin
Aggressive Non Hodgkin Lymphoma
Leukemia-Lymphoma, Adult T-Cell and B-cell
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2009-04-20
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: 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 outcomes:
measure: Time to Response Onset
timeFrame: 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
measure: Duration of Response
timeFrame: 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
measure: Time to Progression
timeFrame: 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
measure: Time to Subsequent Chemotherapy
timeFrame: 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
measure: Progression-free Survival
timeFrame: 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
measure: Overall Survival
timeFrame: 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
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Paris
country: France
facility: Hôpital Saint- Louis
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bologna
country: Italy
facility: Istituto di ematologia e oncologia medica "L. e. A. Seragnoli"
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Modena
country: Italy
facility: Ospedaliero Universitaria de Modena
city: Surquillo
country: Peru
facility: Instituto Nacional de Enfermedades Neoplásicas (INEN)
state: Lima
city: San Juan
country: Puerto Rico
facility: Hospital Español Auxilio Mutuo de Puerto Rico Inc.
city: Barcelona
country: Spain
facility: Hospital Clinico de Barcelona
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Study officials:
affiliation: Institut Gustave Roussy, France
name: Vincent Ribrag, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ribrag V, Caballero D, Ferme 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.