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

Condition(s) targeted: Multiple Myeloma; Diagnosis

Intervention: Autologous transplantation (Procedure)

Phase: Phase 3

Status: Completed

Sponsored by: Azienda Ospedaliera San Giovanni Battista

Official(s) and/or principal investigator(s):
Mario Boccadoro, MD, Principal Investigator, Affiliation: Division of Hematology - University of Torino - A.O.U. San Giovanni Battista

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

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

Primary outcome: 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: Secondary endpoint was time to progression (TTP) defined as the time from the date of diagnosis to relapse or death from progression.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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.

Starting date: February 2002
Last updated: July 31, 2009