POEMS Syndrome Treatment With Lenalidomide

Sponsor

University Hospital, Limoges (Other)

Overall Status

Completed

CT.gov ID

NCT01639898

Collaborator

Ministry of Health, France (Other), Celgene Corporation (Industry)

Enrollment

Locations

Arms

Actual Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

POEMS syndrome is a rare form of B cell dyscrasia combining a proliferation usually of plasma cells, a polyneuropathy, osteocondensing bone lesions and multiple other clinical signs. Lenalidomide appears to be particularly efficient in this pathology.

The investigators propose a phase II multicentre protocol, based on the use of lenalidomide combined with dexamethasone in patients presenting a POEMS syndrome, either de novo or resistant or in relapse.

Patients who can be treated by local radiation or intensive treatment with stem cell support will undergo 2 cycles of the lenalidomide-dexamethasone (Len-Dex) combination before radiation or intensive treatment (Group 1), the other patients will undergo 9 cycles of the Len-Dex combination (Group 2).

A biological study is coupled with this clinical protocol in order to define the best biological markers predicting clinical responses, to better understand the POEMS pathophysiological mechanisms and to set up a bank of samples which can be used to study this rare pathology.

Condition or Disease	Intervention/Treatment	Phase
POEMS Syndrome	Drug: Lenalidomide and dexamethasone Drug: Lenalidomide and dexamethasone	Phase 2

Detailed Description

The investigators propose to simultaneously set up two Phase II therapeutic trials: Trial "2 cycles" and trial "9 cycles" (Fleming plan in one stage).

This will mean prospective multicentre studies, around a treatment with the lenalidomide-dexamethasone combination in patients suffering from POEMS syndrome either de novo, resistant or in relapse.

Both trials carried out in parallel are complementary regarding the eligibility criteria:

Group 1: the "2-cycles" trial will be available to patients who can be treated by radiation or intensive treatment (75 % of cases occurring in front line); they will then undergo 2 cycles of the lenalidomide-dexamethasone combination before radiation or intensive treatment (Group 1).
Group 2 : the "9-cycles" trial will be available to all other front-line patients (25 % of front-line patients) or patients in relapse or resistant, they will undergo 9 cycles of the lenalidomide-dexamethasone combination followed by maintenance therapy with lenalidomide alone for one year (Group 2).

Both these trials carried out within the same study will enable us to answer the question of potential efficacy of lenalidomide in POEMS syndrome and could enable us to draw up a new therapeutic standard.

Main objective:

Group 1: to evaluate the efficacy of the Len-Dex combination on the biological response after 2 cycles in patients with POEMS syndrome who can undergo radiation or intensive treatment.

Group 2: to evaluate the efficacy of the Len-Dex combination on the biological response in patients with POEMS syndrome who cannot be treated by radiation or intensive treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial With Lenalidomide-Dexamethasone Combination in the Treatment of POEMS Syndrome.

Actual Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Jun 1, 2018

Actual Study Completion Date :

Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 ("2-cycles" trial) The "2-cycles" trial will be available to patients who can be treated by radiation or intensive treatment (75 % of cases occurring in front line); they will then undergo 2 cycles of the lenalidomide-dexamethasone combination before radiation or intensive treatment (Group 1).	Drug: Lenalidomide and dexamethasone 2 cycles of the lenalidomide-dexamethasone (Len-Dex) combination before radiation or intensive treatment
Experimental: Group 2 ( "9 cylces" Trial) The "9-cycles" trial will be available to all other front-line patients (25 % of front-line patients) or patients in relapse or resistant, they will undergo 9 cycles of the lenalidomide-dexamethasone combination followed by maintenance therapy with lenalidomide alone for one year (Group 2).	Drug: Lenalidomide and dexamethasone 9 cycles of the Len-Dex combination

Arm

Intervention/Treatment

Experimental: Group 1 ("2-cycles" trial)

The "2-cycles" trial will be available to patients who can be treated by radiation or intensive treatment (75 % of cases occurring in front line); they will then undergo 2 cycles of the lenalidomide-dexamethasone combination before radiation or intensive treatment (Group 1).

Drug: Lenalidomide and dexamethasone

2 cycles of the lenalidomide-dexamethasone (Len-Dex) combination before radiation or intensive treatment

Experimental: Group 2 ( "9 cylces" Trial)

The "9-cycles" trial will be available to all other front-line patients (25 % of front-line patients) or patients in relapse or resistant, they will undergo 9 cycles of the lenalidomide-dexamethasone combination followed by maintenance therapy with lenalidomide alone for one year (Group 2).

Drug: Lenalidomide and dexamethasone

9 cycles of the Len-Dex combination

Outcome Measures

Primary Outcome Measures

Biological outcome [Two months for group 1]
Decrease of monoclonal protein and serum VEGF level
Biological outcome [2, 4 or 6 month for group 2]
Decrease of monoclonal protein and serum VEGF level

Secondary Outcome Measures

Clinical response [2 months]
Evaluation of the neurological (Overall Neuropathy Limitations Scale, Neuropsychological Impairment Scale and 10 m walking test) and other damages responses:

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients suffering from POEMS syndrome (Mayo Clinic criteria)
Patients with a localised disease who can be treated with radiation and those with a disseminated disease and who can be treated intensively will be included in Group 1, all other patients will be included in Group 2.
Patients aged of 18 or more
Patients who do not show uncontrolled thrombosis
Patients who have been duly informed and who have signed a consent form.
Patients must respect all the lenalidomide Pregnancy Prevention Program (PPP) requirements described in appendix of the protocol.
Patients registered with the French National Health System.

Exclusion Criteria:

Women who are pregnant, or suspected to be pregnant or breastfeeding
Pathology not linked with POEMS, contraindicating one of the studied drugs
Patients suffering from a deficiency which does not allow them full understanding of the trial requirements and which could compromise proper consent from the patient and/or observance of the protocol and continuous participation in the trial.
Prior history of malignancy other than POEMS syndrome or active other cancer or other serious illness.
Any contraindication to Revlimid® or to one of its excipient.
Patient with clearance creatinine < 30mL/min.
Hepatic insufficiency
Patient with Absolute Neutrophil count (ANC) < 1,0 x 109/L
Patient with platelet count < 75 x 109/L
Use of any other experimental drug or therapy within 28 days of baseline
Known hypersensitivity to thalidomide
Instable, clinically significant ECG findings
Known positive for HIV, or active infectious hepatitis, type A, B or C
Patients under protection of a legal order.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU d'Angers	Angers	France	49933
2	CHU de Caen	Caen	France	14000
3	CHU de Lille	Lille	France	59037
4	CHU de Limoges	Limoges	France	87042
5	Hospices Civil de Lyon	Lyon	France	69000
6	Centre Léon Bérard	Lyon	France	69373
7	CHU de Nantes	Nantes	France	44093
8	Hôpital Saint-Louis	Paris	France	75010
9	Pitié Salpétrière	Paris	France	75013
10	Hôpital Necker	Paris	France	75743
11	CHU de Toulouse	Toulouse	France	31059