IFM2009-02-Pomalidomide and Dexamethasone Phase 2 Myeloma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2009 by University Hospital, Lille.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01053949
First received: January 21, 2010
Last updated: June 14, 2012
Last verified: November 2009
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: Pomalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

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 [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine response and safety profile of 2 dose-regimens of pomalidomide [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • To determine Safety of pomalidomide and dexamethasone [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • To determine Time to response and Response duration of pomalidomide and dexamethasone [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • To determine Time to disease progression to pomalidomide and dexamethasone [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • Overall Survival of pomalidomide and dexamethasone [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • To determine response in both arms with regards to cytogenetic of the bone marrow tumor plasma cells [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]

Enrollment: 84
Study Start Date: October 2009
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01053949

Locations
France
CHRU-Hôpital Sud, avenue Laennec,
Amiens, France, 80054
Hématologie, Hôpital Avicenne
Bobigny, France, 93009
Hématologie, CHU, avenue G.Clemenceau
Caen, France, 14033
Hématologie Clinique, CHU, Hôpital d'Enfants
Dijon, France, 21000
Hématologie, CHRU, Hôpital A.Michallon
Grenoble, France, 38043
Service des Maladies du Sang, CHRU
Lille, France, 59037
Hôpital Edouard HERRIOT
Lyon, France, 69437
Hématologie, Institut Paoli Calmette
Marseille, France, 13273
Hématologie, CHRU, Hôpitaux de Brabois
Nancy, France, 54511
Maladies du Sang, CHRU, Hôtel Dieu
Nantes, France, 44035
Maladies du Sang, CHU - Hôpital St Antoine
Paris, France, 75571
Service Immuno-Hématologie, Hôpital Saint-Louis
Paris, France, 75475
Service des Maladies du Sang, Hôpital Haut-Levèque
Pessac, France, 33604
Service d'Hématologie, Centre Hospitalier Lyon Sud
Pierre Benite, France, 69495
Hématologie Clinique, Hôpital Robert Debré, CHU Reims
Reims, France, 51092
Hôpital PONTCHAILLOU, CHU de RENNES
Rennes, France, 35033
Médecine Interne, CHRU, Hôpital Sud
Rennes, France, 35056
Hématologie, CHRU, Hôpital Purpan
Toulouse, France, 31059
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
  More Information

No publications provided by University Hospital, Lille

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01053949     History of Changes
Other Study ID Numbers: 2009-013319-36, 2009_28/0924
Study First Received: January 21, 2010
Last Updated: June 14, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
Multiple myeloma
dexamethasone
pomalidomide
response
safety

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Pomalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 30, 2014