Combination Chemotherapy With or Without Thalidomide in Treating Patients With Multiple Myeloma
- Conditions
- Multiple Myeloma and Plasma Cell Neoplasm
- Registration Number
- NCT00028886
- Lead Sponsor
- Commissie Voor Klinisch Toegepast Onderzoek
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect). It is not yet known whether chemotherapy followed by peripheral blood stem cell transplant is more effective with or without thalidomide in treating multiple myeloma.
PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with thalidomide to see how well it works compared with giving combination chemotherapy without thalidomide in treating patients with multiple myeloma.
- Detailed Description
OBJECTIVES:
* Compare the efficacy of doxorubicin, dexamethasone, and high-dose melphalan with versus without thalidomide, in terms of event-free survival, of patients with multiple myeloma.
* Determine the response rate, complete response rate, overall survival, and progression-free survival of patients treated with these regimens.
* Determine the safety and toxicity of thalidomide in combination with intensive chemotherapy in these patients.
* Assess the value of prognostic factors at diagnosis in individual patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and treatment policy (1 course vs 2 courses of high-dose melphalan). Patients are randomized to 1 of 2 treatment arms.
Arm I:
* Patients receive induction chemotherapy (AD) comprising doxorubicin IV on days 1-4 and oral dexamethasone on days 1-4, 9-12, and 17-20. Patients receive oral thalidomide daily beginning on day 1 and continuing until 2 weeks before start of stem cell mobilization. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Patients receive stem cell mobilization with chemotherapy comprising cyclophosphamide IV on day 1 and doxorubicin IV and oral dexamethasone on days 1-4 (CAD). Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until last apheresis.
* Beginning 8-10 weeks after stem cell collection, patients receive low-dose oral thalidomide daily and high-dose melphalan IV on days -3 and -2 as intensification. Patients undergo stem cell infusion on day 0. Patients may receive a second course of high-dose melphalan 2-3 months after the first course, in which case, stem cell infusion follows the second course of melphalan.
* Patients receive maintenance therapy with oral thalidomide daily until disease progression or after 3 months if no response.
* Beginning 2 months after the last course, patients with an HLA-identical sibling donor undergo nonmyeloablative stem cell transplantation after radiotherapy.
Arm II:
* Patients receive induction chemotherapy (VAD) comprising vincristine IV and doxorubicin IV on days 1-4 and dexamethasone on days 1-4, 9-12, and 17-20. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Patients receive stem cell mobilization with CAD chemotherapy as in arm I. G-CSF is given as in arm I.
* Patients receive high-dose melphalan and undergo stem cell infusion as in arm I.
* Patients receive maintenance therapy with interferon alfa SC 3 times weekly until progression or after 3 months if no partial response.
* Beginning 2 months after the last course, patients with an HLA-identical sibling donor undergo nonmyeloablative stem cell transplantation after radiotherapy.
All patients are followed every 6 months for 3 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this study within 4 years.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 450
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Event-free survival
- Secondary Outcome Measures
Name Time Method Overall survival Partial response and complete response Toxicity Progression-free survival
Trial Locations
- Locations (17)
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Isala Klinieken - locatie Sophia
🇳🇱Zwolle, Netherlands
Academisch Medisch Centrum at University of Amsterdam
🇳🇱Amsterdam, Netherlands
Medisch Centrum Leeuwarden - Zuid
🇳🇱Leeuwarden, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
HagaZiekenhuis - Locatie Leyenburg
🇳🇱's-Gravenhage, Netherlands
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Jeroen Bosch Ziekenhuis
🇳🇱's-Hertogenbosch, Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
🇳🇱Amsterdam, Netherlands
Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Universitair Medisch Centrum St. Radboud - Nijmegen
🇳🇱Nijmegen, Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Sint Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands