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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

Phase 2
19 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

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

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.

Inclusion 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

30 months

Safety Issue:


Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:

CHRU-Hôpital Sud d'Amiens-AMIENS


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

October 2009

Completion Date:

August 2013

Related Keywords:

  • Multiple Myeloma
  • Multiple myeloma
  • dexamethasone
  • pomalidomide
  • response
  • safety
  • Multiple Myeloma
  • Neoplasms, Plasma Cell