LeukemiaPhase 2NCT00884286

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

A Phase 2 study testing Aplidin® in people with Leukemia and Lymphoma, run by PharmaMar at 12 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Leukemia, Lymphoma
What is being tested?: Aplidin®
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 67 participants
Where: 12 sitesin 6 countries
Study dates: Dec 2004to Jun 2010
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 9Show fewer

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.

Who cannot join

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.

Show all 21Show fewer

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.

Trial locations and contacts

12 sites in 6 countries.

Country

City, postcode or hospital

12 sites in 6 countries

France3 sites

Centre Hospitalier Lyon Sud
Lyon, 69495
Hôpital Saint- Louis
Paris, 75475
Institut Gustave Roussy
Villejuif, 94805

Other trials in France

Italy3 sites

Istituto di ematologia e oncologia medica "L. e. A. Seragnoli"
Bologna, 40138
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Ospedaliero Universitaria de Modena
Modena, 41100

Other trials in Italy

Spain3 sites

Hospital Clinico de Barcelona
Barcelona, 08036
Hospital Morales Meseguer
Murcia, 3008
Hospital Universitario de Salamanca
Salamanca, 37707

Other trials in Spain

Peru1 site

Instituto Nacional de Enfermedades Neoplásicas (INEN)
Surquillo, Lima region, 34

Other trials in Peru

Puerto Rico1 site

Hospital Español Auxilio Mutuo de Puerto Rico Inc.
San Juan, 00919

Other trials in Puerto Rico

Switzerland1 site

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, CH-6500

Other trials in Switzerland

About this study

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

Read the 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.

Conditions: Leukemia, Lymphoma
Being tested: Aplidin®
Keywords: Aplidin, Aggressive Non Hodgkin Lymphoma, Leukemia-Lymphoma, Adult T-Cell and B-cell
Medical subject headings: Leukemia, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aplidin®Drug
Also called plitidepsin
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.

Study groups in NCT00884286
Study group	Role	What they receive
Arm One	Experimental	Aplidin® given as a 1-hour weekly IV infusion Receives: Drug: Aplidin®

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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 (6)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2004Jun 2010

First posted20 Apr 2009 (estimated)
Study startDec 2004
Primary completionJun 2010
Study completionJun 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 67 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00884286
Sponsor's protocol ID: APL-B-013-02
Status last verified: Feb 2011
First submitted: 17 Apr 2009
Last updated: 25 Apr 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

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.
PubMed 23065525

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00884286
Acronym / sponsor ID: APL-B-013-02
Conditions: Leukemia, Lymphoma
Keywords: Aplidin, Aggressive Non Hodgkin Lymphoma, Leukemia-Lymphoma, Adult T-Cell and B-cell
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 67 participants (actual)
Lead sponsor: PharmaMarIndustry (pharma, biotech, devices)
Study start: Dec 2004
Primary completion: Jun 2010 (actual)
Study completion: Jun 2010 (actual)
First posted: 20 Apr 2009 (estimated)
Results: Posted 29 Mar 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Arm One	Experimental	Drug: Aplidin®Aplidin® given as a 1-hour weekly IV infusion

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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.

Key exclusion criteria (21 listed)

Prior therapy with Aplidin®.
Concomitant therapy with any anti-lymphoproliferative agent
Acute lymphoblastic leukemia.
CNS lymphoma.
HIV-associated lymphoma.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Aplidin®Also: plitidepsinAplidin® 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.	Drug	Arm One

Primary outcome

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).

6 secondary outcomes

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
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
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 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
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
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

Results and safety

Results posted to the registry on 29 Mar 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aplidin® (Cohort Non-cutaneous PTCL)	34	2
Aplidin®(Other Lymphoma)	33	0

Primary outcome: 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. Count of participants. Unit: Participants

Measure	Arm One n = 67
Non-cutaneous PTCL: Complete response	2
Non-cutaneous PTCL: Partial response	4
Non-cutaneous PTCL: Stable Disease	6
Non-cutaneous PTCL: Progressive disease	17
Non-cutaneous PTCL: Not evaluable	5
Other lymphomas: Complete response	0
Other lymphomas: Partial response	0
Other lymphomas: Stable Disease	6

Population analysed: The efficacy and safety analyses were to be performed separately for the subset of treated patients with non-cutaneous Peripheral T-cell Lymphoma (PTCL), and for the subset of treated patients with other lymphomas.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aplidin® (Cohort Non-cutaneous PTCL)	13 of 32 (40.6%)	31 of 32 (96.9%)	10 of 32
Aplidin® (Cohort Other Lymphomas)	11 of 32 (34.4%)	32 of 32 (100%)	10 of 32

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23065525Ribrag 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vincent Ribrag, MD principal investigator

Institut Gustave Roussy, France

12 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aplidin® in people with Leukemia and Lymphoma, run by PharmaMar at 12 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in France, Italy, Spain, Peru, Puerto Rico and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00884286, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2018.