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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00884286

Enrollment

Registered

2009-04-20

Start date

2004-12-31

Completion date

2010-06-30

Last updated

2018-04-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia, Lymphoma

Keywords

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

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.

Interventions

DRUGAplidin®

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 design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate	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

Measure	Time frame	Description
Duration 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 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	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.
Time to Response Onset	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.
Progression-free Survival	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.
Overall Survival	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.
Time to Subsequent Chemotherapy	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.

Countries

France, Italy, Peru, Puerto Rico, Spain, Switzerland

Participant flow

Participants by arm

Arm	Count
Aplidin® (Cohort Non-cutaneous) Aplidin® given as a 1-hour weekly IV infusion 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.	34
Aplidin® (Cohort Other Lymphoma) Aplidin® given as a 1-hour weekly IV infusion 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.	33
Total	67

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Comprised lung carcinoma	0	1
Overall Study	Death	2	2
Overall Study	Not treated	2	1
Overall Study	Physician Decision	1	0
Overall Study	Progressive disease	21	28
Overall Study	Septic shock	1	0
Overall Study	Thrombus in right auricle	1	0
Overall Study	Toxicity	4	1

Baseline characteristics

Characteristic	Aplidin® (Cohort Non-cutaneous)	Aplidin® (Cohort Other Lymphoma)	Total
Age, Customized 17 years	0 Participants	1 Participants	1 Participants
Age, Customized >= 70 years	6 Participants	10 Participants	16 Participants
Age, Customized Between 18 and 49 years	14 Participants	3 Participants	17 Participants
Age, Customized Between 50 and 69 years	14 Participants	19 Participants	33 Participants
Region of Enrollment France	20 Participants	23 Participants	43 Participants
Region of Enrollment Italy	3 Participants	0 Participants	3 Participants
Region of Enrollment Peru	2 Participants	0 Participants	2 Participants
Region of Enrollment Spain	7 Participants	9 Participants	16 Participants
Region of Enrollment Switzerland	2 Participants	1 Participants	3 Participants
Sex: Female, Male Female	24 Participants	22 Participants	46 Participants
Sex: Female, Male Male	10 Participants	11 Participants	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	10 / 32	10 / 32
other Total, other adverse events	31 / 32	32 / 32
serious Total, serious adverse events	13 / 32	11 / 32

Outcome results

Primary

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).