Thalidomide Plus Dexamethasone as Maintenance Therapy for Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Thalidomide Plus Dexamethasone as Maintenance Therapy After Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma: a Multicenter Phase 3 Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01296503
• Other study ID #: GBRAM0001
• Status: Completed
• Phase: Phase 3
• First received: January 27, 2011
• Last updated: February 14, 2011
• Start date: October 2003
• Est. completion date: December 2010

Study information

• Verified date: February 2011
• Source: Grupo de Estudos Multicentricos em Onco-Hematologia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: December 2010
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Thalidomide plus dexamethasone
D+60 after ASCT: randomization in two arms of maintenance: Arm A (dexamethasone alone 40 mg/day for 4 days every 28 days) and Arm B (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
dexamethasone alone 40 mg/day for 4 days every 28 days

Locations

Country	Name	City	State
Brazil	Universidade Estadual de Campinas	Campinas	São Paulo
Brazil	Universidade de São Paulo- Ribeirão Preto	Ribeirão Preto	São Paulo
Brazil	Hospital Universitário Clementino Fraga Filho	Rio de Janeiro
Brazil	Santa Casa de Misericórdia de São Paulo	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Grupo de Estudos Multicentricos em Onco-Hematologia

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free survival	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.	36 months	No
Secondary	Overall survival	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.	36 months	Yes
Secondary	safety of thalidomide	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.	36 months	Yes