IFM2009-02-Pomalidomide and Dexamethasone Phase 2 Myeloma

Sponsor

University Hospital, Lille (Other)

Overall Status

Completed

CT.gov ID

NCT01053949

Collaborator

Celgene Corporation (Industry)

Enrollment

Locations

Arms

Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the response to pomalidomide and dexamethasone in relapse and refractory MM patients who are progressive and did not achieve at least a partial response to bortezomib and lenalidomide. This study will determine the efficacy and toxicity profile of 2 modalities of pomalidomide in patients with advanced myeloma, previously heavily treated characterized with adverse prognostic and that are in desperate need of novel therapeutics.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pomalidomide Drug: Pomalidomide	Phase 2

Detailed Description

Multiple myeloma (MM) is an incurable disease that is characterized by the accumulation of clonal plasma cells in the bone marrow. The median overall survival for patients with MM is approximately 4-5 years. Despite front line treatment approaches, the disease eventually relapses. The recent US Food and Drug Administration (FDA) approvals of bortezomib (2003) and combination lenalidomide plus dexamethasone (2006) therapies for the treatment of previously treated MM has provided effective therapeutic options that give patients with relapsed or refractory MM the prospect for a prolongation of overall and progression-free survival times. However, MM remains an incurable disease. A clear unmet medical need still exists for additional novel therapeutic options for the treatment of previously treated MM.

Pomalidomide belongs to the IMiDs class of compounds which thalidomide is the parent compound and lenalidomide the most recently approved agent. It is derived from thalidomide and shares a number of the beneficial pharmacologic properties with thalidomide. The efficacy of thalidomide has been limited by adverse effects. This toxicity profile seems dose and duration-related, spurring the development of IMiDs, which have the potential of improved potency and reduced toxicity. By modifying the thalidomide structure through the addition of an amino group at the 4 position of the phthaloyl ring to generate pomalidomide, a compound that is up to 50000 times more potent at inhibiting TNF-alpha than thalidomide was formed.

Recently, preliminary efficacy and safety data from an ongoing phase 2 study, led by Martha Lacy, et al, at Mayo Clinic, were presented at the XII International Myeloma Workshop in Washington DC (01 March 2009). The study highlighted a 63 % objective response and a 5% complete response in patients taking pomalidomide (2 mg daily on days 1-28 of a 28-day cycle) plus dexamethasone (40 mg daily on days 1, 8, 15, 22 of each cycle) including patients with lenalidomide resistant refractory multiple myeloma. The results also showed that the treatment was well tolerated. Based on the encouraging data of this study, a phase 1/2b multi-center, randomized, open-label, dose escalation study (dose level from 2 mg to 5 mg daily on days 1-21 of a 28-day cycle)is conducted to determine the MTD of pomalidomide. This ongoing study will evaluate the safety and efficacy of oral pomalidomide alone, and in combination with dexamethasone, in patients with relapsed and refractory MM. The first results obtained in this study demonstrated that the maximum tolerated dose of pomalidomide was 4 mg once per day and highlighted that pomalidomide has significant efficacy in MM and can be safely administered to myeloma patients. Moreover, there are an increasing number of patients who are refractory or did not respond significantly or experienced significant toxicity to either bortezomib or lenalidomide.

Based on these studies, we hypothesized that these patients might benefit from the combination of pomalidomide and dexamethasone. We have therefore designed a multicenter phase 2 randomized open labelled study to determine response to pomalidomide and dexamethasone in relapse and refractory MM patients who are progressive and did not achieve at least a partial response to bortezomib and lenalidomide. This study will determine the efficacy and toxicity profile of 2 modalities of pomalidomide in patients with advanced myeloma, previously heavily treated characterized with adverse prognostic and that are in desperate need of novel therapeutics. This study will be conducted in accordance with "good clinical practice" (GCP) and all applicable regulatory requirements, including, where applicable, the 2008 version of the Declaration of Helsinki.

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter Randomized Open Label Phase II Study of Pomalidomide and Dexamethasone in Relapse and Refractory Multiple Myeloma Patients Who Are Progressive and Did Not Achieve at Least a Partial Response to Bortezomib and Lenalidomide

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Drug on 21 days per 28 days cycle Pomalidomide 4 mg continuous daily oral route on 21 days per 28 days cycle. The proposed dose of dexamethasone is considered standard, 40mg/day once a week.	Drug: Pomalidomide Pomalidomide 4 mg continuous daily oral route on 21 days per 28 days cycle. The proposed dose of dexamethasone is considered standard, 40mg/day once a week. Other Names: Actimid CC-4047
Active Comparator: Drug on 28 days per 28 days cycle Pomalidomide 4 mg continuous daily oral route on 28 days of a 28 days cycle The proposed dose of dexamethasone is considered standard, 40mg/day once a week.	Drug: Pomalidomide Pomalidomide 4 mg continuous daily oral route on 28 days of a 28 days cycle The proposed dose of dexamethasone is considered standard, 40mg/day once a week. Other Names: Actimid CC-4047

Arm

Intervention/Treatment

Active Comparator: Drug on 21 days per 28 days cycle

Pomalidomide 4 mg continuous daily oral route on 21 days per 28 days cycle. The proposed dose of dexamethasone is considered standard, 40mg/day once a week.

Drug: Pomalidomide

Pomalidomide 4 mg continuous daily oral route on 21 days per 28 days cycle. The proposed dose of dexamethasone is considered standard, 40mg/day once a week.

Other Names:

Actimid

CC-4047

Active Comparator: Drug on 28 days per 28 days cycle

Pomalidomide 4 mg continuous daily oral route on 28 days of a 28 days cycle The proposed dose of dexamethasone is considered standard, 40mg/day once a week.

Drug: Pomalidomide

Pomalidomide 4 mg continuous daily oral route on 28 days of a 28 days cycle The proposed dose of dexamethasone is considered standard, 40mg/day once a week.

Other Names:

Actimid

CC-4047

Outcome Measures

Primary Outcome Measures

To determine Response rate to pomalidomide and dexamethasone in MM patients who are progressive and did not achieve at least a partial response to bortezomib and lenalidomide [30 months]

Secondary Outcome Measures

To determine response and safety profile of 2 dose-regimens of pomalidomide [30 months]
To determine Safety of pomalidomide and dexamethasone [30 months]
To determine Time to response and Response duration of pomalidomide and dexamethasone [30 months]
To determine Time to disease progression to pomalidomide and dexamethasone [30 months]
Overall Survival of pomalidomide and dexamethasone [30 months]
To determine response in both arms with regards to cytogenetic of the bone marrow tumor plasma cells [30 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key inclusion criteria:

Must be able to understand and voluntarily sign an informed consent form
Must be able to adhere to the study visit schedule and other protocol requirements
18 years>=Age
Life expectancy>6 months
Patients must have Symptomatic and Progressive Myeloma following bortezomib and/or lenalidomide treatment, defined as detailed in protocol.
Patients must have a clearly detectable and quantifiable monoclonal M-component value*
ECOG performance status score of 0,1,or 2
Adequate bone marrow function,documented within 72 hours prior to treatment without transfusion or growth factor support,defined as*
Wash out period of at least 2 weeks from previous antitumor therapy or any investigational treatment
Able to take antithrombotic medicines such as Low molecular weight heparin or Aspirin 75mg
Subjects affiliated with an appropriate social security system
Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy
Agree not to share study medication with another person and to return all unused study drug to the investigator
Female subjects of childbearing potential* must:Understand that the study medication is expected to have a teratogenic risk-Agree to use,and be able to comply with, effective contraception* without interruption,4 weeks before starting study drug,throughout the entire duration of study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy,even if she has amenorrhoea.This applies unless the subject commits to absolute and continued abstinence on a monthly basis-Understand that even if she has amenorrhea,she must follow all the advice on effective contraception-She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy-Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/mL on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks-Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment,except in the case of confirmed tubal sterilization. These pregnancy tests should be performed on the day of the study visit or in the 3 days prior to the study visit.This requirement also applies to women of childbearing potential who practice complete and continued abstinence
Male subjects must:Agree to use condoms throughout study drug therapy,during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception Agree not to donate semen during study drug therapy and for one week after end of study drug therapy

Exclusion Criteria:

Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation
Pregnant or breast feeding females
Use of any other experimental drug or therapy within 15 days of screening.
Known positive for HIV or infectious hepatitis,type A, B or C.
Patients with non-secretory MM
Prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for >= 3 years.Exceptions include the following*
Prior local irradiation within two weeks before screening
Evidence of central nervous system involvement
Any>grade 2 toxicity unresolved
Peripheral neuropathy>=Grade 2
Known Hypersensitivity to Thalidomide,Lenalidomide or Dexamethasone
Ongoing active infection,especially ongoing pneumonitis
Ongoing Cardiac dysfunction
Inability or unwillingness to comply with birth control requirements
Unable to take antithrombotic medicines at study entry
Unable to take corticotherapy at study entry
Refusal to participate in the study
Persons protected by a legal regime(guardianship,trusteeship)

(*)=described in protocol

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHRU-Hôpital Sud, avenue Laennec,	Amiens	France	80054
2	Hématologie, Hôpital Avicenne	Bobigny	France	93009
3	Hématologie, CHU, avenue G.Clemenceau	Caen	France	14033
4	Hématologie Clinique, CHU, Hôpital d'Enfants	Dijon	France	21000
5	Hématologie, CHRU, Hôpital A.Michallon	Grenoble	France	38043
6	Service des Maladies du Sang, CHRU	Lille	France	59037
7	Hôpital Edouard HERRIOT	Lyon	France	69437
8	Hématologie, Institut Paoli Calmette	Marseille	France	13273
9	Hématologie, CHRU, Hôpitaux de Brabois	Nancy	France	54511
10	Maladies du Sang, CHRU, Hôtel Dieu	Nantes	France	44035
11	Service Immuno-Hématologie, Hôpital Saint-Louis	Paris	France	75475
12	Maladies du Sang, CHU - Hôpital St Antoine	Paris	France	75571
13	Service des Maladies du Sang, Hôpital Haut-Levèque	Pessac	France	33604
14	Service d'Hématologie, Centre Hospitalier Lyon Sud	Pierre Benite	France	69495
15	Hématologie Clinique, Hôpital Robert Debré, CHU Reims	Reims	France	51092
16	Hôpital PONTCHAILLOU, CHU de RENNES	Rennes	France	35033
17	Médecine Interne, CHRU, Hôpital Sud	Rennes	France	35056
18	Hématologie, CHRU, Hôpital Purpan	Toulouse	France	31059
19	Onco-Hématologie, CHRU- Hôpital Bretonneau	Tours	France	37044

Sponsors and Collaborators

University Hospital, Lille
Celgene Corporation

Investigators

Principal Investigator: Bruno ROYER, MD PhD, CHRU-Hôpital Sud d'Amiens-AMIENS
Principal Investigator: Philippe RODON, MD PhD, Centre Hospitalier de Blois -BLOIS
Principal Investigator: Sabine BRECHIGNAC, MD PhD, Hôpital Avicenne-Bobigny- PARIS
Principal Investigator: Gerard MARIT, MD PhD, Hôpital Haut-Levèque de Pessac-BORDEAUX
Principal Investigator: Christian BERTHOU, MD PhD, Service d'Hématologie Clinique, CHU Morvan, BREST
Principal Investigator: Margaret MACRO, MD PhD, Hématologie, CHU, CAEN
Principal Investigator: Denis CAILLOT, MD PhD, Hématologie Clinique, CHU, Hôpital d'Enfants, DIJON
Principal Investigator: Brigitte PEGOURIE, MD PhD, Hématologie, CHRU, Hôpital A.Michallon, GRENOBLE
Principal Investigator: Catherine TRAULLE, MD PhD, Service d'Hématologie, Centre Hospitalier Lyon Sud, PIERRE BENIT
Principal Investigator: Anne Marie STOPPA, MD PhD, Hématologie, Institut Paoli Calmette, MARSEILLE
Principal Investigator: Cyrille HULIN, MD PhD, Hématologie, CHRU, Hôpitaux de Brabois, VANDOEUVRE
Principal Investigator: Philippe MOREAU, MD PhD, Maladies du Sang, CHRU, Hôtel Dieu, NANTES
Principal Investigator: Jean-Gabriel FUZIBET, MD PhD, Médecine Interne, Oncologie, Hôpital de l'Archet 1, NICE
Principal Investigator: Bernard GROSBOIS, MD PhD, Médecine Interne, CHRU, Hôpital Sud, RENNES
Principal Investigator: Brigitte KOLB, MD PfD, Hématologie Clinique, Hôpital Robert Debré, CHU REIMS
Principal Investigator: Laurent GARDERET, MD PhD, Maladies du Sang, CHU - Hôpital St Antoine, PARIS
Principal Investigator: Jean-Paul FERMAND, MD PhD, Service Immuno-Hématologie, Hôpital Saint-Louis, PARIS
Principal Investigator: Michel ATTAL, MD PhD, Hématologie, CHRU, Hôpital Purpan, TOULOUSE
Principal Investigator: Lofti BENBOUBKER, MD PhD, Onco-Hématologie, CHRU- Hôpital Bretonneau, TOURS
Study Director: Xavier Leleu, MD PhD, Service des maladies du sang, CHRU de Lille