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

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Aplidin®
Sponsored by
PharmaMar
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Aplidin, Aggressive Non Hodgkin Lymphoma, Leukemia-Lymphoma, Adult T-Cell and B-cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Centre Hospitalier Lyon Sud
  • Hôpital Saint- Louis
  • Institut Gustave Roussy
  • Istituto di ematologia e oncologia medica "L. e. A. Seragnoli"
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Ospedaliero Universitaria de Modena
  • Instituto Nacional de Enfermedades Neoplásicas (INEN)
  • Hospital Español Auxilio Mutuo de Puerto Rico Inc.
  • Hospital Clinico de Barcelona
  • Hospital Morales Meseguer
  • Hospital Universitario de Salamanca
  • Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm One

Arm Description

Aplidin® given as a 1-hour weekly IV infusion

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
Time to Progression
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 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
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
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.

Full Information

First Posted
April 17, 2009
Last Updated
March 28, 2018
Sponsor
PharmaMar
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1. Study Identification

Unique Protocol Identification Number
NCT00884286
Brief Title
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

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
December 2004 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PharmaMar

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
Aplidin, Aggressive Non Hodgkin Lymphoma, Leukemia-Lymphoma, Adult T-Cell and B-cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm One
Arm Type
Experimental
Arm Description
Aplidin® given as a 1-hour weekly IV infusion
Intervention Type
Drug
Intervention Name(s)
Aplidin®
Other Intervention Name(s)
plitidepsin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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).
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
Secondary Outcome Measure Information:
Title
Time to Response Onset
Description
Time to response onset was defined as the time from the first day of plitidepsin treatment to the first documentation 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
Title
Duration of Response
Description
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 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
Title
Time to Progression
Description
Time to progression (TTP) was to be calculated from the first day of plitidepsin treatment to the date of disease 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
Title
Time to Subsequent Chemotherapy
Description
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.
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
Title
Progression-free Survival
Description
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.
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
Title
Overall Survival
Description
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincent Ribrag, MD
Organizational Affiliation
Institut Gustave Roussy, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Lyon Sud
City
Lyon
ZIP/Postal Code
69495
Country
France
Facility Name
Hôpital Saint- Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Istituto di ematologia e oncologia medica "L. e. A. Seragnoli"
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Ospedaliero Universitaria de Modena
City
Modena
ZIP/Postal Code
41100
Country
Italy
Facility Name
Instituto Nacional de Enfermedades Neoplásicas (INEN)
City
Surquillo
State/Province
Lima
ZIP/Postal Code
34
Country
Peru
Facility Name
Hospital Español Auxilio Mutuo de Puerto Rico Inc.
City
San Juan
ZIP/Postal Code
00919
Country
Puerto Rico
Facility Name
Hospital Clinico de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Morales Meseguer
City
Murcia
ZIP/Postal Code
3008
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37707
Country
Spain
Facility Name
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
City
Bellinzona
ZIP/Postal Code
CH-6500
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23065525
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.
Results Reference
derived

Learn more about this trial

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

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