IFM2009-02-Pomalidomide and Dexamethasone Phase 2 Myeloma

Phase 2

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: Pomalidomide

• Registration Number: NCT01053949
• Lead Sponsor: University Hospital, Lille

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.

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 Timeline

• Study Start: 2009-10
• Study First Submitted: 2010-01-21
• Study First Submitted QC: 2010-01-21
• Study First Posted: 2010-01-22
• Primary Completion: 2014-04
• Study Completion: 2015-04
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-03
• Last Update Posted: 2015-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Drug on 28 days per 28 days cycle	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.
Drug on 21 days per 28 days cycle	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.

Primary Outcome Measures

Name	Time	Method
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

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

Trial Locations

Locations (19)

CHRU-Hôpital Sud, avenue Laennec,; 🇫🇷 Amiens, France

Hématologie, Hôpital Avicenne; 🇫🇷 Bobigny, France

Hématologie, CHU, avenue G.Clemenceau; 🇫🇷 Caen, France

Hématologie Clinique, CHU, Hôpital d'Enfants; 🇫🇷 Dijon, France

Hématologie, CHRU, Hôpital A.Michallon; 🇫🇷 Grenoble, France

Service des Maladies du Sang, CHRU; 🇫🇷 Lille, France

Hôpital Edouard HERRIOT; 🇫🇷 Lyon, France

Hématologie, Institut Paoli Calmette; 🇫🇷 Marseille, France

Hématologie, CHRU, Hôpitaux de Brabois; 🇫🇷 Nancy, France

Maladies du Sang, CHRU, Hôtel Dieu; 🇫🇷 Nantes, France

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