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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Drug: Aplidin®

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: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69495
    • Centre Hospitalier Lyon Sud
  • Paris, France, 75475
    • Hôpital Saint- Louis
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Italy
  • Bologna, Italy, 40138
    • Istituto di Ematologia e Oncologia Medica "L. e. A. Seragnoli"
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Modena, Italy, 41100
    • Ospedaliero Universitaria de Modena
• Peru
  • Lima
    • Surquillo, Lima, Peru, 34
      • Instituto Nacional de Enfermedades Neoplásicas (INEN)
• Puerto Rico
  • San Juan, Puerto Rico, 00919
    • Hospital Español Auxilio Mutuo de Puerto Rico Inc.
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínico de Barcelona
  • Murcia, Spain, 3008
    • Hospital Morales Meseguer
  • Salamanca, Spain, 37707
    • Hospital Universitario de Salamanca
• Switzerland
  • Bellinzona, Switzerland, CH-6500
    • Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm One; Aplidin® given as a 1-hour weekly IV infusion	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 Names: plitidepsin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PharmaMar
• Investigators: Principal Investigator: Vincent Ribrag, MD, Institut Gustave Roussy, France

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: April 17, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (ESTIMATE): April 20, 2009

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2018
• Last Update Submitted That Met QC Criteria: March 28, 2018
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Aplidin; Aggressive Non Hodgkin Lymphoma; Leukemia-Lymphoma, Adult T-Cell and B-cell
• Additional Relevant MeSH Terms: Behavioral Symptoms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Aggression; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: APL-B-013-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO