Multicenter cooperative phase 3 study for the treatment of recently diagnosed multiple myeloma risk based strategy

• Grant number: 03/05350-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2004
• End date: September 30, 2008
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carmino Antonio de Souza
• Grantee: Carmino Antonio de Souza
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Pesquisadores principais: Vania Tietsche de Moraes Hungria

Abstract

To validate stratification by risk, proposing therapeutic strategies that vary in intensity. To evaluate the role of thalidomide in association with dexamethasone (low risk) or DCEP (high risk) as a consolidation scheme after the autologous transplant. Study design and duration: this is a prospective, comparative multicentric, randomized and open study with two treatment groups, in accordance with risk stratification. Patients who do not show cytogenetic alterations involving chromosome 13 (analyzed by the FISH technique and conventional cytogenetics) and/or have a beta-2-microglobulin dose of 2.5 mg/l or less will be considered low risk patients, while high risk will be defined as the presence of both alterations above. Treatment for the low risk group will consist of three chemotherapy cycles with the VAD scheme (vincristine, doxorubicin, and dexamethasone) administered through the outpatients clinic, followed by mobilizing the hematopoietic stem cells of the peripheral blood with cyclophosphamide (4g/m2) and G-CSF (10 ?g/kg/day). After collecting a minimum of 4 x 108 cells CD34+/Kg of weight, the patient will be submitted to an autologous transplant, whose conditioning regime will be 200 mg/m2 of melphalan. After D+100 of the transplant, patients will be randomized into two consolidation groups: thalidomide (200 mg/d) + dexamethasone (40 mg/d for 4 days once a month), in a total of 12 months, or dexamethasone (40 mg/d for 4 days, per month), in a total of 12 months. If there is relapse or progression of the disease, the patients will receive a second autologous transplant. Those who do not have enough cells collected (previous collection or new mobilization) will receive three cycles of monthly chemotherapy with the DCEP scheme (dexamethasone 40 mg/day for 4 days, cyclophosphamide 400 mg/m2 for 4 days, cisplatin 10 mg/m2 for 4 days and etoposide 40 mg/m2 for 4 days) with or without thalidomide (200 mg/d), depending on whether or not they have used it before. For the high risk group, treatment will differ after the autologous transplant. Patients under 60 and identical HLA donors will receive a non-myeloablative allogenic transplant, and their conditioning regime will be the melphalan scheme (70 mg/m2 /day for 2 days) and Fludarabine (30 mg/m2 /day for 4 days). As consolidation, these patients will receive infusions of lymphocytes from the donor on days D+60, 90, and 120 if they do not present acute GvHD. For patients above 60 or without compatible HLA donor, a second autologous transplant will be offered with the same conditioning scheme as with the first. After D+100 of transplant, patients treated with the second autologous transplant will be randomized to receive chemotherapy with DCEP every three months, during a year (totaling four cycles) in one arm, and DCEP with thalidomide 200 mg/d for a year in the other consolidation arm. This study will last five years and shall include no less than 71 low risk patients, in each maintenance arm. Response rates, global survival and survival free from the disease will be analyzed in both groups, just as patients quality of life will be evaluated in the various phases of the protocol. (AU)