This phase II trial studies how well combination chemotherapy with or without bortezomib works in treating patients with classical Hodgkin lymphoma that has come back or does not respond to prior treatment. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib is designed to block a protein that plays a role in cell function and growth. Bortezomib may cause cancer cells to die. It is not yet known if combination chemotherapy with or without bortezomib may work better in treating patients with classical Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. To determine the objective response rate (ORR), partial remissions (PR), and complete remissions (CR) after 3 cycles of bortezomib plus ifosfamide, carboplatin, and etoposide (ICE) (BICE) versus ICE in patients with relapsed/refractory classical Hodgkin lymphoma (cHL). II. To evaluate 2-year progression-free survival (PFS) in patients treated with 3 cycles of BICE versus ICE. SECONDARY OBJECTIVES: I. To compare positron emission tomography (PET) scan response after 3 cycles of BICE versus ICE chemotherapy. II. To compare serum levels of tumor necrosis factor (TNF) proteins (a proliferation-inducing ligand \[APRIL\], B lymphocyte stimulator \[BLyS\], soluble \[s\]CD30, and CD40L) and CC thymus and activation-related cytokine (TARC) at baseline and after 3 cycles of BICE versus ICE chemotherapy. III. To correlate baseline cytokine/chemokine levels with response to therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive bortezomib intravenously (IV) over 5 seconds on days 1 and 4, ifosfamide IV continuously over 24 hours on day 1, carboplatin IV over 1 hour on day 1, and etoposide IV over 2 hours on days 1-3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive ifosfamide, carboplatin and etoposide as in Arm A. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
M D Anderson Cancer Center
Houston, Texas, United States
Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
Response rates for Bortezomib, Ifosfamide, Carboplatin, Etoposide (BICE) and Ifosfamide, Carboplatin, Etoposide (ICE) treatment groups were assessed by the 1999 International Working Group (IWG)(CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: From baseline to 3 cycles of treatment
Progression Free Survival (PFS) Rate at 12 Months
Progression free survival time is defined as the time interval from treatment start to progression or death due to any cause whichever happens first. Participants will be censored at the last follow-up date, if an event(progression/death) is not observed during the follow-up.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival (OS) Rate at 24 Months
Overall Survival is time from date of treatment start until date of death due to any cause or last Follow-up within 24 months.
Time frame: 24 months
PET Scan Response After 3 Cycles of BICE Versus ICE Chemotherapy.
Response rates for BICE and ICE treatment groups will be assessed by 1999 IWG (CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria.
Time frame: Baseline up to 1 year
Serum Levels of Tumor Necrosis Factor (TNF) Proteins (APRIL, BLyS, sCD30, and CD40L) and CC Thymus and Activation-related Cytokine (TARC) at Baseline and After 3 Cycles of BICE Versus ICE Chemotherapy
Time frame: November 2009 and December 2010
Baseline Cytokine/Chemokine Levels With Response to Therapy.
Time frame: 106 weeks/13 months/426 days
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