S0833, Bortezomib, Thalidomide, Lenalidomide, Combination Chemotherapy, and Autologous Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma
NCT ID: NCT01055301
Last Updated: 2015-03-06
Study Results
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Basic Information
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WITHDRAWN
PHASE2
INTERVENTIONAL
2011-07-31
2011-07-31
Brief Summary
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PURPOSE: This phase II trial is studying how well giving bortezomib, thalidomide, and lenalidomide together with combination chemotherapy and autologous stem cell transplant works in treating patients with newly diagnosed multiple myeloma.
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Detailed Description
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Primary
* To assess progression-free survival (PFS) at 3 years in patients with newly diagnosed multiple myeloma (MM) treated with modified Total Therapy 3 (TT3).
Secondary
* To estimate the frequency and severity of toxicities associated with this treatment strategy in these patients.
Correlative
* To perform gene expression profiling on CD138+ purified MM cells and unseparated bone marrow biopsy samples to identify the bone marrow micro-environment signature.
* To determine whether the 70-gene model, developed in the Arkansas Total Therapy 2 (TT2) and validated in the Arkansas TT3 study, also applies to the cooperative group setting.
* Determine whether the novel finding in TT3 of the prognostically favorable suppression of a micro-environment-associated gene, MAG1, also applies to the cooperative group setting.
* Once in complete remission, determine whether the MAG signatures can return to a normal individual's signature as an indication of profound tumor cytoreduction with durable PFS.
OUTLINE: This is a multicenter study.
* Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11; oral thalidomide and oral dexamethasone on days 1-4; and cisplatin IV continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV continuously, and etoposide IV continuously on days 1-4.
* Peripheral blood stem cell (PBSC) collection: Beginning within 2 months after completion of induction therapy, patients undergo PBSC collection until an adequate number of cells are collected. Patients with persistent disease after completion of induction therapy proceed to bridging therapy after adequate stem cells are collected. Patients not requiring bridging therapy proceed directly to transplant.
* Bridging therapy: Patients receive oral thalidomide on days 1-21 and oral dexamethasone on days 1, 8, and 15. Treatment repeats every 21 days for 1-2 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to transplant.
* First autologous PBSC transplantation: Beginning within 6 weeks to 3 months after completion of induction therapy (or ≥ 1 week after completion of bridging therapy), patients receive bortezomib IV on days -4 and -1 and melphalan IV, oral thalidomide, and oral dexamethasone on days -4 to -1. Patients undergo autologous PBSC transplantation on day 0.
* Inter-transplant bridging therapy: Patients with persistent disease after completion of the first autologous PBSC transplant receive bridging therapy as above and then proceed to the second transplant. Patients not requiring bridging therapy proceed directly to the second transplant.
* Second autologous PBSC transplantation: Beginning within 6 months after the first PBSC transplant, patients receive bortezomib, melphalan, thalidomide, and dexamethasone and undergo autologous PBSC as in the first transplant. Patients who skip the second transplant (due to medical or insurance reasons or refusal) proceed to consolidation therapy.
* Consolidation therapy: Beginning within 6 months after the last transplant, patients receive bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin hydrochloride, cyclophosphamide, and etoposide as in induction therapy.
* Post-consolidation bridging therapy: Patients with persistent disease after completion of consolidation therapy receive oral thalidomide on days 1-21 and oral dexamethasone on days 1, 8, and 15. Patients then proceed to maintenance therapy. Patients not requiring bridging therapy proceed directly to maintenance therapy.
* Maintenance therapy: Beginning within 4 months after completion of consolidation therapy or post-consolidation bridging therapy, patients receive bortezomib IV and oral dexamethasone on days 1, 8, 15, and 22 and oral lenalidomide on days 1-20. Courses repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity.
Blood and bone marrow samples may be collected at baseline and periodically during study for gene expression profile analysis.
After completion of study therapy, patients are followed up periodically for up to 7 years.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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treatment
Ind (1cycle):
bort 1mg/m2 IV/SQ D1,4,8,11 D1-4: thalid 200mg/d \& dex 20mg/d PO; cisplatin \& dox 10mg/m2/d, cyclophos 400mg/m2/d, etoposide 40mg/m2/d contIV; enoxaparin 40mg/d SQ prn.
PBSC Coll: at recovery per local standard
Bridging (before/between trans/after Cons):
thal 50mg/d D1-21 \& dex 20mg D1,8,15 PO
Tandem Trans (x2):
bort 1mg/m2 IV/SQ D-4,-1 D-4to-1: mel 50 mg/m2 IV, thal 200mg/d \& dex 40mg/d PO PBSC \>/=200x10\^6 cells
Cons (1cycle):
same as Ind except cis/dox 7.5mg/m2/d, cyclo 300mg/m2/d, no enox
Maint(\</= 3 yrs):
D1,8,15,22:bort 1mg/m2 IV/SQ, dex 20mg/d PO; len 20mg/d PO D1-20
bortezomib
cisplatin
cyclophosphamide
dexamethasone
doxorubicin hydrochloride
etoposide
lenalidomide
melphalan
thalidomide
gene expression analysis
microarray analysis
laboratory biomarker analysis
autologous-autologous tandem hematopoietic stem cell transplantation
Interventions
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bortezomib
cisplatin
cyclophosphamide
dexamethasone
doxorubicin hydrochloride
etoposide
lenalidomide
melphalan
thalidomide
gene expression analysis
microarray analysis
laboratory biomarker analysis
autologous-autologous tandem hematopoietic stem cell transplantation
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Newly diagnosed active multiple myeloma (MM)
* Measurable disease
* Non-secretory disease allowed provided patient has ≥ 20% plasmacytosis or multiple (\> 3) focal plasmacytomas on skeletal survey and/or MRI
PATIENT CHARACTERISTICS:
* Zubrod performance status (PS) 0-2 (Zubrod PS 3-4 allowed if based solely on bone pain)
* ANC ≥ 1,500/mm\^3\*
* Platelet count ≥ 150,000/mm\^3\*
* Serum creatinine clearance of ≥ 60 mL/min
* Patients with creatinine clearance of \< 60 mL/min receive a lower dose of melphalan
* No patients receiving or planning to receive dialysis
* Total bilirubin ≤ 1.5 times upper limit of normal
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Must be fully aware of the teratogenic potential of thalidomide
* Must be willing to comply with the FDA-mandated S.T.E.P.S. program
* Ejection fraction \> 40% as measured by MUGA scan or two-dimensional ECHO
* No peripheral neuropathy ≥ grade 2 per CTCAE v. 4.0
* No known hypersensitivity to bortezomib, boron, or mannitol
* No uncontrolled diabetes defined as fasting glucose level \> 200 mg/dL on at least more than two occasions or more that two serum random blood levels \> 300 mg/dL despite adequate treatment
* Patients with a history of diabetes mellitus requiring treatment should be on a stable regimen and have their blood glucose closely monitored
* No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment within the past year NOTE: \*Unless myeloma-related marrow infiltration is documented, defined as ≥ 30% marrow cellularity with 50% of the cells being malignant plasma cells.
PRIOR CONCURRENT THERAPY:
* At least 4 weeks since prior chemotherapy or radiotherapy
* No more than 1 prior course of chemotherapy for MM
* Prior chemotherapy must not have included melphalan
* No prior radiotherapy to large area of the pelvis (more than half of the pelvis)
* Prior radiotherapy for symptomatic localized bone lesions or impending cord compression allowed
18 Years
65 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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Muneer H. Abidi, MD
Role: PRINCIPAL_INVESTIGATOR
Barbara Ann Karmanos Cancer Institute
Locations
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Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, United States
Hematology-Oncology Clinic
Baton Rouge, Louisiana, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States
Island Hospital Cancer Care Center at Island Hospital
Anacortes, Washington, United States
St. Joseph Cancer Center
Bellingham, Washington, United States
Olympic Hematology and Oncology
Bremerton, Washington, United States
Highline Medical Center Cancer Center
Burien, Washington, United States
Columbia Basin Hematology
Kennewick, Washington, United States
Skagit Valley Hospital Cancer Care Center
Mount Vernon, Washington, United States
Harrison Poulsbo Hematology and Onocology
Poulsbo, Washington, United States
Harborview Medical Center
Seattle, Washington, United States
Minor and James Medical, PLLC
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Group Health Central Hospital
Seattle, Washington, United States
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States
North Puget Oncology at United General Hospital
Sedro-Woolley, Washington, United States
Cancer Care Northwest - Spokane South
Spokane, Washington, United States
Evergreen Hematology and Oncology, PS
Spokane, Washington, United States
Wenatchee Valley Medical Center
Wenatchee, Washington, United States
Countries
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Other Identifiers
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S0833
Identifier Type: OTHER
Identifier Source: secondary_id
S0833
Identifier Type: -
Identifier Source: org_study_id
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