Primary Treatment of Waldenstrom's Macroglobulinemia with Bortezomib (Velcade®) and Rituximab followed by autologous stem cell collection
The main goal of this clinical research study is to learn if Velcade ® (bortezomib) given with rituximab can help to control WM. This drug combination will allow researchers to collect your stem cells in case it is possible to transplant the stem cells as treatment if your WM gets worse. Researchers will also look at the safety and tolerability of this drug combination followed by treatment with other drug combinations.
Disease Group: Myeloma
Treatment Agent: Bortezomib
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: not applicable
Return Visit: Within 1 week prior to the start of each cycle of chemotherapy, and every 3 months thereafter until partial response or better is achieved then follow up every 6 months
Home Care: None
Primary Objectives To assess response rate in newly diagnosed patients with Waldenstrom's Macroglobulinemia treated with bortezomib and rituximab. To assess ability to collect stem cells after treatment with bortezomib and rituximab in newly diagnosed patients with Waldenstrom's Macroglobulinemia. Secondary Objectives To assess overall response rate to treatment with bortezomib and rituximab followed by cladribine, cyclophosphamide and rituximab in newly diagnosed patients with Waldenstrom's Macroglobulinemia To assess time to progression and time to retreatment, following treatment with bortezomib and rituximab followed by cladribine, cyclophosphamide and rituximab in newly diagnosed patients with Waldenstrom's Macroglobulinemia To assess toxicity of treatment with bortezomib and rituximab in newly diagnosed patients with Waldenstrom's Macroglobulinemia.
IRB Review and Approval Date: 05/03/2006
Recruitment Status: Closed
Projected Accrual: N/A
1) Patients with symptomatic macroglobulinemic lymphoma who have had no
prior treatment, or whose prior treatment has been limited to steroids
and/or alpha-interferon, are eligible. Macroglobulinemic lymphoma
includes patients with either biopsy proven clonal lymphocytic or
lymphoplasmacytic proliferation and monoclonal IgM. Also included are
symptomatic patients with clonal proliferation producing a pathologic
monoclonal IgM that causes cryoglobulinemia, peripheral neuropathy or
cold agglutinin hemolytic anemia.
2) Patients must have acceptable liver function (total bilirubin < 2.5mg/dL) and renal function (creatinine < 2.0mg/dL). Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass) that might reverse with improvement of disease.
3) Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
4) Male subject agrees to use an acceptable method for contraception for the duration of the study.
5) Patients must voluntarily sign an informed consent form indicating that they are aware of the investigational nature of the study, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
6) Patient has a heart rate (HR) of greater than or equal to 50 bpm.
1) Patient has a platelet count of <30x10^9/L within 28 days before
enrollment unless due to >/= 75% marrow infiltration by
macroglobulinemic lymphoma or splenomegaly.
2) Patient has an absolute neutrophil count of <1.0x10^9/L within 28 days before enrollment unless due to >/= 75% marrow infiltration by macroglobulinemic lymphoma.
3) Patient has a calculated or measured creatinine >/= to 2.0mg/dL on baseline evaluation. Patients with imparied renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, uteteral obstruction due to mass).
4) Patient has >/= Grade 2 peripheral neuropathy on baseline evaluation.
5) Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
6) Patient has hypersensitivity to boron, mannitol, or murine proteins.
7) Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urine Beta -human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
8) Patient has received other investigational drugs within 14 days before enrollment
9) Patient has a serious medical or psychiatric illness that is likely to interfere with participation in this clinical study.
10) Eastern Cooperative Oncology Group (ECOG) performance status of > 2.
11) Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years and are considered by their physician to be at less than 30 % risk of relapse.
12) Patient with a lifetime cumulative dose of > 450 mg/m^2 of anthracyclines.
13) Patients with an active hepatitis B infection.