S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia
NCT ID: NCT00723658
Last Updated: 2015-03-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE2
INTERVENTIONAL
2008-09-30
Brief Summary
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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.
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Detailed Description
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Primary
* 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.
Secondary
* 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.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Observation
Non-symptomatic patients are monitored monthly for 3 months, then every 3 months thereafter.
No interventions assigned to this group
Treatment
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
1. 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
2. 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
rituximab
bortezomib
carmustine
cisplatin
cyclophosphamide
cytarabine
dexamethasone
doxorubicin hydrochloride
etoposide
melphalan
thalidomide
autologous-autologous tandem hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
Interventions
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rituximab
bortezomib
carmustine
cisplatin
cyclophosphamide
cytarabine
dexamethasone
doxorubicin hydrochloride
etoposide
melphalan
thalidomide
autologous-autologous tandem hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
Eligibility Criteria
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Inclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
SWOG Cancer Research Network
NETWORK
Responsible Party
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Principal Investigators
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Gordan Srkalovic, MD, PhD
Role: STUDY_CHAIR
Sparrow Regional Cancer Center
Locations
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Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States
Reid Hospital & Health Care Services
Richmond, Indiana, United States
Lawrence Memorial Hospital
Lawrence, Kansas, United States
Wesley Medical Center
Wichita, Kansas, United States
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, United States
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
Dearborn, Michigan, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Genesys Hurley Cancer Institute
Flint, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States
Foote Memorial Hospital
Jackson, Michigan, United States
Sparrow Regional Cancer Center
Lansing, Michigan, United States
St. Mary Mercy Hospital
Livonia, Michigan, United States
St. Joseph Mercy Oakland
Pontiac, Michigan, United States
Mercy Regional Cancer Center at Mercy Hospital
Port Huron, Michigan, United States
Seton Cancer Institute at Saint Mary's - Saginaw
Saginaw, Michigan, United States
St. John Macomb Hospital
Warren, Michigan, United States
Grandview Hospital
Dayton, Ohio, United States
Good Samaritan Hospital
Dayton, Ohio, United States
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States
CCOP - Dayton
Dayton, Ohio, United States
Blanchard Valley Medical Associates
Findlay, Ohio, United States
Middletown Regional Hospital
Franklin, Ohio, United States
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States
Clinton Memorial Hospital
Wilmington, Ohio, United States
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States
Countries
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Other Identifiers
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S0629
Identifier Type: OTHER
Identifier Source: secondary_id
S0629
Identifier Type: -
Identifier Source: org_study_id
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