S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia
Lymphoma
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring Waldenström macroglobulinemia
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of Waldenstrom macroglobulinemia (WM)
- Measurable disease as determined by IgM protein quantification
Must be registered to the treatment portion of the study within 28 days of experiencing disease-related symptoms* AND must present with ≥ 1 of the following disease-related symptoms:
- Hemoglobin ≤ 11 g/dL
- Platelet count ≤ 100,000/mm³
- Marked tumor mass, defined as lymphadenopathy > 2 cm, palpable hepatomegaly, splenomegaly, or significant marrow involvement (> 50%)
- Serum albumin < 2.5 g/dL
- Persistently elevated beta-2-microglobulin > 3.0 mg/L in the absence of renal impairment or active infections
- Presence of B symptoms (i.e., fever, night sweats, or weight loss of > 10% from baseline)
- Appearance of new or worsening neuropathy manifested by numbness and tingling or pain
- Symptomatic cryoglobulinemia (i.e., Raynaud phenomenon, skin ulcers, cold urticaria, or skin necrosis)
- Symptoms of hyperviscosity, if measured viscosity > 4 cp (i.e., new headaches, vertigo, ataxia, dizziness with or without evident causes of changes in funduscopic exam, including retinal vein engorgement, hemorrhages, or exudates)
- NOTE: *Appearance of any of the above symptoms caused by WM with no other obvious cause is a trigger for treatment initiation. Symptoms need not persist for any specified time frame.
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-2 (Zubrod performance status 3 allowed provided it is based solely on morbidity due to WM)
- ANC > 1,500/mm³ (unless more marked cytopenias can be explained by marked marrow involvement or autoimmune myelosuppression)
- Serum creatinine < 3 mg/dL
- Creatinine clearance > 30 mL/min
- SGOT/SGPT < 2 times upper limit of normal
- Direct bilirubin < 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception according to the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) program
Ejection fraction ≥ 50% by ECHO or MUGA scan
- Patients with evidence of amyloidosis (i.e., periorbital perforation, proteinuria not attributable to Bence-Jones protein, unexplained arrhythmias, increased liver function tests, peripheral neuropathy, carpal tunnel syndrome, and/or macroglossia) must have an ECHO, rather than MUGA, performed to evaluate for cardiac amyloidosis (septal thickness, diastolic dysfunction, granular sparkling, or low-voltage QRS complexes)
- No myocardial infarction within the past 6 months
- No unstable angina
- No difficult-to-control congestive heart failure or cardiac arrhythmias
- No uncontrolled hypertension
- No peripheral neuropathy ≥ grade 2
- No history of multi-infarced dementia or multiple strokes
- No known hypersensitivity to boron or mannitol
- No hepatitis B or C positivity
- No HIV positivity
- No other prior malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
- At least 28 days since prior chemotherapy and/or radiotherapy and recovered
- No prior bortezomib
- No concurrent glucocorticoids unless used to control autoimmune disease associated with WM
- Concurrent participation in the Myeloma Specimen Repository study allowed
Sites / Locations
- Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
- St. Francis Hospital and Health Centers - Beech Grove Campus
- Reid Hospital & Health Care Services
- Lawrence Memorial Hospital
- Wesley Medical Center
- Saint Joseph Mercy Cancer Center
- CCOP - Michigan Cancer Research Consortium
- Oakwood Cancer Center at Oakwood Hospital and Medical Center
- Barbara Ann Karmanos Cancer Institute
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Van Elslander Cancer Center at St. John Hospital and Medical Center
- Foote Memorial Hospital
- Sparrow Regional Cancer Center
- St. Mary Mercy Hospital
- St. Joseph Mercy Oakland
- Mercy Regional Cancer Center at Mercy Hospital
- Seton Cancer Institute at Saint Mary's - Saginaw
- St. John Macomb Hospital
- Grandview Hospital
- Good Samaritan Hospital
- David L. Rike Cancer Center at Miami Valley Hospital
- CCOP - Dayton
- Blanchard Valley Medical Associates
- Middletown Regional Hospital
- Charles F. Kettering Memorial Hospital
- UVMC Cancer Care Center at Upper Valley Medical Center
- Clinton Memorial Hospital
- Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Arms of the Study
Arm 1
Arm 2
No Intervention
Experimental
Observation
Treatment
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 st Trans: mel 200 mg/m2 IV D-1 bortezomib 1.3 mg/m2 IV D-4, -1 PBSC >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 500 ml IV D-1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1 nd Trans: BCNU 300 mg/m2 IV D-5 etoposide 200 mg/m2 IV D-5 to -2 AraC 400 mg/m2 IV D-5 to -2 mel 140 mg/m2 IV D-1 PBSC infusion >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 150 ml/hr IV D-5 to -1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1