A Randomized Phase II Study of Bortezomib Plus ICE (BICE) Versus Standard ICE for Patients with Relapsed/Refractory Classical Hodgkin Lymphoma
Michelle A. Fanale
The goal of this clinical research study is to learn if bortezomib when given in combination with ifosfamide, carboplatin, and etoposide (a routine chemotherapy combination called ICE) can help to control Hodgkin's lymphoma better than ICE when given alone. The safety of this drug combination will also be studied.
Disease Group: Lymphoma
Treatment Agent: Bortezomib,Carboplatin,Etoposide,Ifosfamide,MESNA
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: Patients will be hospitalized for chemotherapy every 2 to 4 weeks for up to a ;maximum of 6 cycles. It is anticipated that patients will remain in the ;hospital for on average 4 to 6 days.
Sponsor: Millennium Pharmaceuticals - Supporter only (Investigator-initiated study)
Return Visit: Screening, Pre-Treatment -3 days prior to each cycle 1 through 3, Day 1- Day 5 of cycle 1 through 3, Intercycle between each cycle (weekly), Response Assessment, Follow up every 4 months for 2 years
Home Care: None
Primary: 1. To determine the objective response rate (ORR), partial remissions (PR), and complete remissions (CR) after 3 cycles of bortezomib plus ICE (BICE) versus ICE in patients with relapsed/refractory classical Hodgkin lymphoma (cHL). 2. To evaluate 2-year progression-free survival (PFS) in patients treated with 3 cycles of BICE versus ICE. Secondary: 1. To compare PET scan response after 3 cycles of BICE versus ICE chemotherapy. 2. To compare 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. 3. To correlate baseline cytokine/chemokine levels with response to therapy.
IRB Review and Approval Date: 08/24/2009
Recruitment Status: Closed
Projected Accrual: N/A
1) Relapsed or refractory classical Hodgkin lymphoma
2) Patients must have received a front-line standard anthracycline- containing regimen, such as ABVD, Stanford V, or BEACOPP.
3) Bi-dimensionally measurable disease with at least 1 lesion >= 2.0 cm in a single dimension.
4) Patients must meet the following required baseline laboratory data: a) absolute neutrophil count (ANC) >= 1,500/microL, b) platelet count >= 100,000/ microL, c) hemoglobin >= 8 g/dL, d) serum bilirubin < 2.0 mg/dL, e) alkaline phosphatase < 2 x upper limits of normal (ULN), f) AST and ALT < 2 x ULN, g) serum creatinine <= 1.5 mg/dL.
5) Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
6) Age >= 16 years.
7) Females of childbearing potential must have a negative serum beta-hCG pregnancy test and must agree to use 2 highly effective contraceptive methods (hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after completion of protocol treatment. Females of non-childbearing potential are those who are postmenopausal for greater than 1 year or whom have had a bilateral tubal ligation or hysterectomy.
8) Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 3 months after completion of protocol treatment.
9) Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
1) Lymphocyte predominant Hodgkin lymphoma histology.
2) More than one prior chemotherapy regimen.
3) Prior autologous or allogeneic stem cell transplant.
4) Presence of CNS involvement with Hodgkin lymphoma.
5) Known HIV infection or AIDS.
6) Active Hepatitis B or C infection or history of cirrhosis.
7) Grade 2 or greater peripheral neuropathy within 14 days of enrollment.
8) Hypersensitivity to boron or mannitol.
9) Prior bortezomib therapy.
10) Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or squamous intraepithelial lesion on PAP smear, or treated prostate cancer with a stable PSA) for which the patient has not been disease-free for at least 3 years.
11) Patients with congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria.
12) Patients with a myocardial infarction 6 months prior to enrollment, uncontrolled angina, severe uncontrolled ventricular arrthymias, or ECG evidence of acute ischemia or active conduction system abnormalities.
13) Patient with other medical or psychiatric illness that is likely to interfere with participation in this clinical study.
14) Female subject that is pregnant or breast-feeding.
15) Patient that has received other investigational drugs within 14 days of enrollment.
16) Patients using concurrent therapy with corticosteroids at greater than or equal to 20 mg/day of prednisone equivalent.
17) Patients with active systemic bacterial, viral, or fungal infections that have required IV antimicrobials within 4 weeks prior to protocol treatment.
Information and next steps
Michelle A. Fanale
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