S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease
- To assess the progression-free and overall survival of patients with symptomatic
Waldenstrom macroglobulinemia treated with bortezomib, dexamethasone, thalidomide,
cisplatin, doxorubicin hydrochloride, cyclophosphamide, and etoposide (VDT-PACE) in
combination with rituximab, followed by single or tandem autologous peripheral blood
stem cell transplantation and maintenance therapy.
- To assess the confirmed and unconfirmed response in patients treated with this regimen.
- To evaluate the feasibility and toxicity of this regimen in these patients.
- To correlate the time to symptom development and overall survival with standard
prognostic factors and cytopenias.
- To examine the natural history of Waldenstrom macroglobulinemia.
- To identify, in a preliminary fashion, biological correlates that may relate to
progression or to symptomatic disease.
OUTLINE: This is a multicenter study. Patients with asymptomatic disease at study entry
proceed directly to observation. Patients with symptomatic disease at study entry proceed
directly to induction therapy.
- Observation: Patients with asymptomatic disease undergo observation monthly for 3
months and then every 3 months for up to 3 years. Patients who develop symptomatic
disease proceed to induction therapy within 28 days of onset of disease symptoms.
Patients who continue to have asymptomatic disease after 3 years of observation are
removed from the study.
- Induction therapy: Patients receive oral dexamethasone and oral thalidomide on days
1-4; cisplatin IV, doxorubicin hydrochloride IV, cyclophosphamide IV, and etoposide IV
continuously on days 1-4; bortezomib IV on days 1, 4, 8, and 11; and rituximab IV on
days 1, 8, and 15. Treatment repeats every 6-8 weeks for 2 courses in the absence of
disease progression or unacceptable toxicity.
- Peripheral blood stem cell (PBSC) collection: Patients receive filgrastim (G-CSF) IV
beginning on day 9 of course 1 of induction therapy and continuing until WBC counts are
adequate for apheresis. Patients also receive G-CSF IV beginning on day 6 of course 2
of induction therapy and continuing until apheresis is complete.
- First autologous PBSC transplantation*: Beginning approximately 4-6 weeks after the
completion of induction therapy, patients receive conditioning therapy comprising
high-dose melphalan IV and bortezomib IV on days -4 and -1. Patients undergo autologous
PBSC transplantation on day 0 NOTE: *Patients who will receive a single transplant (for
medical, insurance, or other reasons) will not receive melphalan and bortezomib, but
will receive conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM)
and will proceed to Maintenance Therapy.
- Second autologous PBSC transplantation: Beginning approximately 56-90 days after the
first transplant, patients receive conditioning therapy comprising carmustine IV over 2
hours on day -5; etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to
-2; and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day
- Maintenance therapy: Beginning after platelet counts recover, patients receive
bortezomib IV on days 1, 4, 8, and 11 and rituximab IV over 2 hours on day 11.
Treatment repeats every 3 months for 2 years in the absence of disease progression or
After completion of study treatment, patients are followed every 6 months for up to 5 years.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival at 3 years
Gordan Srkalovic, MD, PhD
Sparrow Regional Cancer Center
United States: Federal Government
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|
|Hurley Medical Center||Flint, Michigan 48503|
|CCOP - Michigan Cancer Research Consortium||Ann Arbor, Michigan 48106|
|Saint Joseph Mercy Cancer Center||Ann Arbor, Michigan 48106-0995|
|Oakwood Cancer Center at Oakwood Hospital and Medical Center||Dearborn, Michigan 48123-2500|
|Genesys Hurley Cancer Institute||Flint, Michigan 48503|
|Van Elslander Cancer Center at St. John Hospital and Medical Center||Grosse Pointe Woods, Michigan 48236|
|Sparrow Regional Cancer Center||Lansing, Michigan 48912-1811|
|St. John Macomb Hospital||Warren, Michigan 48093|
|CCOP - Dayton||Kettering, Ohio 45429|
|Wesley Medical Center||Wichita, Kansas 67214|
|Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center||Hartford, Connecticut 06105|
|St. Francis Hospital and Health Centers - Beech Grove Campus||Beech Grove, Indiana 46107|
|Grandview Hospital||Dayton, Ohio 45405|
|David L. Rike Cancer Center at Miami Valley Hospital||Dayton, Ohio 45409|
|Good Samaritan Hospital||Dayton, Ohio 45406|
|Blanchard Valley Medical Associates||Findlay, Ohio 45840|
|Charles F. Kettering Memorial Hospital||Kettering, Ohio 45429|
|Middletown Regional Hospital||Middletown, Ohio 45044|
|UVMC Cancer Care Center at Upper Valley Medical Center||Troy, Ohio 45373-1300|
|Ruth G. McMillan Cancer Center at Greene Memorial Hospital||Xenia, Ohio 45385|
|Reid Hospital & Health Care Services||Richmond, Indiana 47374|
|Lawrence Memorial Hospital||Lawrence, Kansas 66044|
|Foote Memorial Hospital||Jackson, Michigan 49201|
|St. Mary Mercy Hospital||Livonia, Michigan 48154|
|St. Joseph Mercy Oakland||Pontiac, Michigan 48341-2985|
|Mercy Regional Cancer Center at Mercy Hospital||Port Huron, Michigan 48060|
|Seton Cancer Institute at Saint Mary's - Saginaw||Saginaw, Michigan 48601|
|Clinton Memorial Hospital||Wilmington, Ohio 45177|