Melphalan 200 mg/m2 Versus Melphalan 100 mg/m2 in Newly Diagnosed Myeloma Patients

Study Overview
=================
Brief Summary
-----------------
In this study will be randomised before induction treatment either to receive two courses of melphalan 200 mg/m2 (MEL200) or two courses of melphalan 100 mg/m2 (MEL100). Informed consent will be obtained upon enrolment. Inclusion criteria included: diagnosis of untreated Durie e Salmon stage IIA-IIIB measurable multiple myeloma; age < 65 years. Exclusion criteria included: prior treatment for myeloma; abnormal cardiac function, defined as systolic ejection fraction <50%; abnormal pulmonary spirometry test; serum bilirubins > 2.5 times normal and ALAT and/or ASAT > 2 times normal; seropositivity for HIV, HCV or HBV, active non-hematologic malignancies. Induction therapy, PBSC mobilization, and autografting Initial treatment plan included induction chemotherapy with 2 courses of vincristine, 1 mg/m2 on day 1, adriamycin, 50 mg/m2 on day 1, and dexamethasone, 40mg/day days 1-4, administered 28 days apart, followed by peripheral blood stem cell (PBSC) mobilisation and harvest after 1 or 2 cycles of cyclophosphamide, 4 g/m2, and G-CSF, 10 ug/kg given i.v. or subcutaneously. After at least one month from PBSC collection, autografting consisted of melphalan, 200 mg/m2 or melphalan, 100 mg/m2, on day -2, and cryopreserved PBSC infusion on day 0. Patients received G-CSF, 5 ug/kg, from days +3 until neutrophil count > 1000/ul were achieved. Supportive care and toxicity grading Following autografting, all patients received standard prophylaxis against bacterial and fungal infections; herpes simplex and varicella-zoster virus reactivation; and Pneumocystis carinii. Cytomegalovirus CMV reactivation was monitored through levels of CMV antigenemia and/or serum CMV DNA levels and treated with ganciclovir or foscarnet as clinically indicated. Standard criteria (Common Toxicity Criteria version 3.0) were used for grading hematological and non-hematological toxicity.

Official Title
-----------------
GISMM2001: Melphalan 200 mg/m2 Versus Melphalan 100 mg/m2 in Newly Diagnosed Myeloma Patients: a Prospective, Multi-center Phase III Study

Conditions
-----------------
Multiple Myeloma, Diagnosis

Intervention / Treatment
-----------------
* Procedure: Autologous transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria included: diagnosis of untreated Durie & Salmon stage IIA-IIIB measurable multiple myeloma; age < 65 years. Exclusion criteria included: prior treatment for myeloma; abnormal cardiac function, defined as systolic ejection fraction <50%; abnormal pulmonary spirometry test; serum bilirubins > 2.5 times normal and ALAT and/or ASAT > 2 times normal; seropositivity for HIV, HCV or HBV, active non-hematologic malignancies.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mel100<br> | Procedure: Autologous transplantation<br>* Tandem autologous transplantation Melphalan 100 mg/m2 versus Melphalan 200 mg/m2<br>|
| Experimental: Mel200<br> | Procedure: Autologous transplantation<br>* Tandem autologous transplantation Melphalan 100 mg/m2 versus Melphalan 200 mg/m2<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoints of the study were Overall Survival defined as the time from diagnosis until death from any cause; Progression Free Survival defined as the time from diagnosis until death from any cause or date of first relapse or progression. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoint was time to progression (TTP) defined as the time from the date of diagnosis to relapse or death from progression. |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Myeloma, Melphalan, Autologous transplantation