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

• ClinicalTrials.gov Identifier: NCT00884286
• Recruitment Status: Completed
• First Posted: April 20, 2009
• Results First Posted: March 29, 2018
• Last Update Posted: April 25, 2018
• Sponsor: PharmaMar
• Information provided by (Responsible Party): PharmaMar

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia; Lymphoma	Drug: Aplidin®	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: December 2004
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

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 Name: plitidepsin

Outcome Measures

Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

6. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

France

Centre Hospitalier Lyon Sud

Lyon, France, 69495

Hôpital Saint- Louis

Paris, France, 75475

Institut Gustave Roussy

Villejuif, France, 94805

Italy

Istituto di ematologia e oncologia medica "L. e. A. Seragnoli"

Bologna, Italy, 40138

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, Italy, 20133

Ospedaliero Universitaria de Modena

Modena, Italy, 41100

Peru

Instituto Nacional de Enfermedades Neoplásicas (INEN)

Surquillo, Lima, Peru, 34

Puerto Rico

Hospital Español Auxilio Mutuo de Puerto Rico Inc.

San Juan, Puerto Rico, 00919

Spain

Hospital Clinico de Barcelona

Barcelona, Spain, 08036

Hospital Morales Meseguer

Murcia, Spain, 3008

Hospital Universitario de Salamanca

Salamanca, Spain, 37707

Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, Switzerland, CH-6500

Sponsors and Collaborators

PharmaMar

Investigators

• Principal Investigator: Vincent Ribrag, MD; Institut Gustave Roussy, France

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: PharmaMar
• ClinicalTrials.gov Identifier: NCT00884286
• Other Study ID Numbers: APL-B-013-02
• First Posted: April 20, 2009
• Results First Posted: March 29, 2018
• Last Update Posted: April 25, 2018
• Last Verified: February 2011

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by PharmaMar:

Aplidin; Aggressive Non Hodgkin Lymphoma; Leukemia-Lymphoma, Adult T-Cell and B-cell

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Aggression; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Behavioral Symptoms