Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial
I. To assess the feasibility and toxicities of tandem cycle ablative therapy consisting
first of high-dose melphalan and then escalating doses of fractionated total marrow
irradiation (TMI) using helical tomotherapy in patients with advanced multiple myeloma.
II. To establish the maximum tolerated dose of TMI using helical tomotherapy. III. To assess
response rate, progression free and over-all survival following treatment with tandem cycle
ablative therapy consisting first of high-dose melphalan and then escalating doses of TMI
using helical tomotherapy with Dexamethasone/Thalidomide maintenance therapy in patients
with advanced multiple myeloma.
IV. To assess the feasibility of adding decadron and thalidomide as maintenance following
the second cycle of high-dose therapy.
I. To perform cytogenetic, gene rearrangement, and fluorescence in situ hybridization (FISH)
studies on baseline and post-treatment bone marrow and blood specimens and correlate the
presence/persistence of these features with treatment outcome.
II. To bank/develop cell lines developed for future investigations of tumor biology, and for
potential assessment of efficacy of novel therapeutic agents.
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
PRIMING AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Patients also
receive filgrastim IV or subcutaneously daily beginning 24 hours after the administration
of cyclophosphamide and continuing until apheresis is complete. Patients undergo apheresis
until an adequate number of peripheral blood stem cells are collected.
Course 1: Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1.
Patients then undergo autologous PBSC transplantation on day 0 and receive filgrastim IV or
subcutaneously beginning on day 5 and continuing until blood counts recover.
Course 2: Beginning 6-18 weeks later, patients undergo TMI once or twice daily on days -4 to
-1. Patients then undergo autologous peripheral blood stem cell transplant and receive
filgrastim IV or subcutaneously beginning on day 5 and continuing until blood counts
MAINTENANCE THERAPY: Beginning within 6-8 weeks of day 0 of course 2 (TMI), patients receive
oral lenalidomide daily. Courses repeat every 28 days for approximately 3 years in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days, every 6 months for 1
year, and then annually for at least 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
At 3 years
City of Hope Medical Center
United States: Institutional Review Board
City of Hope 04064
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