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

Azienda Ospedaliera San Giovanni Battista

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma; Diagnosis

Treatments: Procedure: Autologous transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT00950768

GISMM2001

Details and patient eligibility

About

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.

Enrollment: 298 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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298 participants in 2 patient groups

Mel100

Active Comparator group

Treatment:

Procedure: Autologous transplantation

Mel200

Experimental group

Treatment:

Procedure: Autologous transplantation