S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia
RATIONALE: Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. Giving combination chemotherapy together with bortezomib, thalidomide, and rituximab before an autologous peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
PURPOSE: This observational and phase II trial is studying how well giving combination chemotherapy together with bortezomib, thalidomide, and rituximab followed by two autologous peripheral blood stem cell transplants works in treating patients with Waldenstrom macroglobulinemia.
Drug: doxorubicin hydrochloride
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease|
- Progression-free survival at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Response rate (complete response, very good partial response, and partial response) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Standard prognostic factors and other potential correlates that may relate to progression, symptomatic disease, and/or survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2008|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
No Intervention: Observation
Non-symptomatic patients are monitored monthly for 3 months, then every 3 months thereafter.
Symptomatic pts: 2 cycles VTDPACE+R:
dex 40 mg PO D1-4 thalid 200 mg PO D1-4 cisplatin 10 mg/m2 IV D1-4 dox 10 mg/m2 IV D1-4 cyclophos 400 mg/m2 IV D1-4 etoposide 40 mg/m2 IV D1-4 bortezomib 1.0 mg/m2 IV D1,4,8,11 ritux 375 mg/m2 IV D1,8,15 lovenox 40 mg/d SQ D1-platelets >50,000/mcl GCSF 10 mcg/kg/d IV D9-WBC <2,000/mcl apheresis >/= 20x10^6 when WBC and CD34 within normal range, up to 4 cycles
|Biological: rituximab Drug: bortezomib Drug: carmustine Drug: cisplatin Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: melphalan Drug: thalidomide Procedure: autologous-autologous tandem hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation|
- 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 0.
- 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 unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for up to 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00723658
|United States, Connecticut|
|Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center|
|Hartford, Connecticut, United States, 06105|
|United States, Indiana|
|St. Francis Hospital and Health Centers - Beech Grove Campus|
|Beech Grove, Indiana, United States, 46107|
|Reid Hospital & Health Care Services|
|Richmond, Indiana, United States, 47374|
|United States, Kansas|
|Lawrence Memorial Hospital|
|Lawrence, Kansas, United States, 66044|
|Wesley Medical Center|
|Wichita, Kansas, United States, 67214|
|United States, Michigan|
|CCOP - Michigan Cancer Research Consortium|
|Ann Arbor, Michigan, United States, 48106|
|Saint Joseph Mercy Cancer Center|
|Ann Arbor, Michigan, United States, 48106-0995|
|Oakwood Cancer Center at Oakwood Hospital and Medical Center|
|Dearborn, Michigan, United States, 48123-2500|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201-1379|
|Genesys Hurley Cancer Institute|
|Flint, Michigan, United States, 48503|
|Hurley Medical Center|
|Flint, Michigan, United States, 48503|
|Van Elslander Cancer Center at St. John Hospital and Medical Center|
|Grosse Pointe Woods, Michigan, United States, 48236|
|Foote Memorial Hospital|
|Jackson, Michigan, United States, 49201|
|Sparrow Regional Cancer Center|
|Lansing, Michigan, United States, 48912-1811|
|St. Mary Mercy Hospital|
|Livonia, Michigan, United States, 48154|
|St. Joseph Mercy Oakland|
|Pontiac, Michigan, United States, 48341-2985|
|Mercy Regional Cancer Center at Mercy Hospital|
|Port Huron, Michigan, United States, 48060|
|Seton Cancer Institute at Saint Mary's - Saginaw|
|Saginaw, Michigan, United States, 48601|
|St. John Macomb Hospital|
|Warren, Michigan, United States, 48093|
|United States, Ohio|
|Dayton, Ohio, United States, 45405|
|CCOP - Dayton|
|Dayton, Ohio, United States, 45420|
|Good Samaritan Hospital|
|Dayton, Ohio, United States, 45406|
|David L. Rike Cancer Center at Miami Valley Hospital|
|Dayton, Ohio, United States, 45409|
|Blanchard Valley Medical Associates|
|Findlay, Ohio, United States, 45840|
|Middletown Regional Hospital|
|Franklin, Ohio, United States, 45005-1066|
|Charles F. Kettering Memorial Hospital|
|Kettering, Ohio, United States, 45429|
|UVMC Cancer Care Center at Upper Valley Medical Center|
|Troy, Ohio, United States, 45373-1300|
|Clinton Memorial Hospital|
|Wilmington, Ohio, United States, 45177|
|Ruth G. McMillan Cancer Center at Greene Memorial Hospital|
|Xenia, Ohio, United States, 45385|
|Study Chair:||Gordan Srkalovic, MD, PhD||Sparrow Regional Cancer Center|