GISMM2001: Melphalan 200 mg/m2 Versus Melphalan 100 mg/m2 in Newly Diagnosed Myeloma Patients: a Prospective, Multi-center Phase III Study
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 298
- Primary Endpoint
- 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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •diagnosis of untreated Durie & Salmon stage IIA-IIIB measurable multiple myeloma;
- •age < 65 years.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
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 Outcomes
- Secondary endpoint was time to progression (TTP) defined as the time from the date of diagnosis to relapse or death from progression.