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Thalidomide Plus Dexamethasone as Maintenance Therapy for Multiple Myeloma

Phase 3
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT01296503
Lead Sponsor
Grupo de Estudos Multicentricos em Onco-Hematologia
Brief Summary

This multicenter, prospective, randomized trial was designed to evaluate the role of thalidomide with or without dexamethasone as a maintenance therapy for multiple myeloma patients after a single autologous stem cell transplantation.

Detailed Description

Patients were recruited prior to receiving induction therapy, and randomization in a 1:1 ratio occurred on day 60 post-autologous stem cell transplantation. The treatment consisted of the following four phases:

1. induction with 3-5 cycles of vincristine plus doxorrubicin and dexamethasone (VAD) every 21-28 days: vincristine 0.4 mg , doxorubicin 9 mg/m² and oral dexamethasone 40 mg daily for 4 days;

2. cyclophosphamide (4 g/m2 ) plus filgrastim (G-CSF) (5 μg/kg twice a day) for stem cell mobilization;

3. melphalan (200 mg/m2 ) and one autologous stem cell transplant (ASCT);

4. Sixty days (D +60) after ASCT: RANDOMIZATION in two arms of maintenance: Arm A (oral dexamethasone alone 40 mg/d for 4 days every 28 days) and Arm B (dexamethasone plus thalidomide 200 mg daily by mouth) for 12 months or until disease progression.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
213
Inclusion Criteria
  • symptomatic multiple myeloma in accordance with the International Myeloma Working Group criteria;
  • age 18-70 years;
  • Performance status 0-2 by the Eastern Cooperative Oncology Group (ECOG) criteria;
  • normal hepatic function, defined as serum bilirubin <3 mg/dl and alanine aminotransferase(ALT) and asparagin aminotransferase (AST) <4x normal.
Exclusion Criteria
  • evidence of disease progression after ASCT;
  • cardiac dysfunction (systolic ejection fraction <50%);
  • chronic respiratory disease (carbon monoxide diffusion <50% of normal).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Thalidomide and Dexamethasone (Arm B)Thalidomide plus dexamethasoneD+60 after ASCT: dexamethasone plus thalidomide 200 mg by mouth daily for 12 months or until disease progression. The dose of thalidomide could be reduced if the patient experienced grade 2 or higher adverse events. In this case, thalidomide was discontinued and re-challenged at a lower dose after resolution of the adverse event.
Dexamethasone (Arm A)DexamethasoneSixty days (D+60) after ASCT: randomization in two arms of maintenance: Arm A (dexamethasone alone 40 mg/day for 4 days every 28 days)
Primary Outcome Measures
NameTimeMethod
Progression Free survival36 months

Primary endpoint: progression free survival (PFS) PFS was defined as the time between randomization and any documentation of relapse, progression, or death by any cause.

Secondary Outcome Measures
NameTimeMethod
Overall survival36 months

Secondary endpoints: overall survival (OS) was defined as the interval from randomization to death (or the last follow-up for surviving patients). For patients who were not randomized, OS was calculated from the date of diagnosis until the date of death or last follow-up.

safety of thalidomide36 months

The number of patients experiencing adverse events grade 3 or 4 were compared between treatment arms. Adverse events were classified as defined by the National Cancer Institute Common Toxicity Criteria, version 2. Safety evaluations were focused especially on neurological symptoms and the development of deep venous thrombosis (DVT). Adverse events evaluations were performed at the time of response assessment and whenever a new clinical manifestation suggestive of toxicity appeared.

Trial Locations

Locations (4)

Universidade Estadual de Campinas

🇧🇷

Campinas, São Paulo, Brazil

Santa Casa de Misericórdia de São Paulo

🇧🇷

São Paulo, Brazil

Universidade de São Paulo- Ribeirão Preto

🇧🇷

Ribeirão Preto, São Paulo, Brazil

Hospital Universitário Clementino Fraga Filho

🇧🇷

Rio de Janeiro, Brazil

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