Early Response-adapted Intensification of Induction Chemotherapy in Patients With Newly Diagnosed Multiple Myeloma (MM)

Study Overview
=================
Brief Summary
-----------------
In this study, the investigators will analyze the long-term outcomes of remission and survival, and identify those with primary resistant disease as more likely to benefit from CTD (thalidomide, cyclophosphamide, dexamethasone) and early intensification of Vel-CD (bortezomib and CD) as induction chemotherapy followed by autologous stem cell transplantation for the patients with newly diagnosed multiple myeloma.

Detailed Description
-----------------
This study aims to assess the efficacy and toxicities of CTD and Vel-CD induction followed by high-dose therapy with autologous stem cell transplantation as a first line treatment for the patients with multiple myeloma.The investigators already investigated the thalidomide-based chemotherapy in patients with newly diagnosed MM. The combined regimen consisted of cyclophosphamide, thalidomide and dexamethasone (CTD) for induction treatment. CTD chemotherapy resulted in a favorable response with 79.4% overall response rate including 42.6% complete response (CR) or very good partial complete response (VGPR), and tolerable toxicity in MM patients. Moreover, CTD chemotherapy did not affect the yield of the stem cell collection.The investigators also published that the clinical efficacy and safety of a four-drug combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone was assessed for patients with relapsed or refractory multiple myeloma Vel-CTD chemotherapy.

Official Title
-----------------
Early Response-adapted Intensification of Induction Chemotherapy in Patients With Newly Diagnosed Multiple Myeloma (MM) Who Are Eligible for Autologous Stem Cell Transplantation: Multicenter Phase 2 Study

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Thalidomide, cyclophosphamide, dexamethasone, bortezomib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed MM Aged between 18 and 65 years old With following measurable lesions (serum M-protein ≥ 1 g/dL or urine M-protein ≥ 400 mg/day, or free light chain ≥ 100 mg/L) Exclusion Criteria: Smoldering or indolent myeloma ECOG performance status > 3 point Known hypersensitivity to cyclophosphamide, thalidomide or dexamethasone Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3 Uncontrolled or severe cardiovascular disease, including MI within 6 months of enrolment, NYHA Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis, cardiac ejection fraction <0.5 : Severe conduction disorder : Hypotension (sitting systolic BP ≤ 100 mmHg and/or sitting diastolic BP ≤ 60 mmHg Impaired hepatic function (AST or ALT ≥ x 3 upper normal, T-bilirubin ≥ x 2 upper normal) Creatinine clearance < 20 ml/min Corrected serum calcium ≥ 14 mg/dL Sepsis or current active infection Pregnancy or breast feeding Uncontrolled Diabetes Mellitus Previous history of Recurrent DVT or pulmonary embolism Active ulcers detected by gastroscopy Serious medical or psychiatric illness likely to interfere with participation in this clinical study. Receipt of extensive radiation therapy within 4 weeks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Thalidomide, cyclophosphamide, dexamethasone, bortezomib|Induction therapy with CTD regimen for 4 cycles Thalidomide 50-100 mg P.O. HS D 1 28 Cyclophosphamide 150 mg/m² P.O. D 1 4 Dexamethasone 20 mg/ m² IV or P.O. D 1 4, 15-18 Repeated every 28 days Intensification with Vel-CD regimen for 4 cycles (patients who fail to achieve more than PR after 2 cycles of CTD) Velcade 1.3 mg/m2 IV D1, 4, 8, 11 Cyclophosphamide 150 mg/m² P.O. D 1 4 Dexamethasone 20 mg/ m² IV or P.O. D1, 4, 8, 11 Repeated every 21 days Bactrim prophylaxis during dexamethasone administration Acyclovir prophylaxis during velcade administration Aspirin medication during thalidomide administration|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate for induction chemotherapy |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
age under 65, Previous untreated