In This SectionTexas Health Research & Education Institute
Disease or Condition
Phase II Study for the Evaluation of Bendamustine, Bortezomib and Dexamethasone (BBD) in the First-Line Treatment of Patients with Multiple Myeloma Who Are Not Candidates for High Dose Chemotherapy
To evaluate an investigative drug, bendamustine, in combination with two approved chemotherapy drugs, in the first-line treatment of multiple myeloma.
Patients must meet the criteria for symptomatic multiple myeloma as defined by the International Myeloma Working Group (see Appendix A). The following criteria must be met except as noted: clonal bone marrow plasma cells =10% presence of serum and/or urinary monoclonal protein (except in patients with true non-secretory multiple myeloma) and evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (CRAB) 1 or more of the following required:
a. hypercalcemia: serum calcium =11.5 mg/100 mL
b. renal insufficiency: serum creatinine >2 mg/dL (173 µmol/L or more)
c. anemia: normochromic, normocytic with a hemoglobin value of >2 g/100 mL below the lower limit of normal or a hemoglobin value of <10 g/100 ml
d. bone lesions: lytic lesions, severe osteopenia or pathologic fractures
Patients should not be considered candidates for high dose therapy/autologous stem cell transplantation due to coexistent medical conditions, advanced age, poor performance status, refusal of high dose chemotherapy, or other reasons as judged by the patient and/or physician.
ECOG Performance Status 0-2. (Appendix B).
Patient must have ANC 1000/L and platelets 50,000/L (patients with platelets 30,000/L are eligible if thrombocytopenia is felt to be due to extensive bone marrow involvement with myeloma).
Patients with adequate organ function as measured by:
Renal: Serum creatinine <2.0 mg/dL or a calculated or measured creatinine clearance of >30 mL/minute.
Hepatic: Total bilirubin < 1.5 x ULN and ALT and AST <2.5 x the ULN (<5 x ULN for patients with liver involvement).
Patients must have measurable disease requiring systemic therapy.
At least one of the three following measurements defines measurable disease: Serum M-protein =1 g/dl (=10 g/l) Urine M-protein =200 mg/24 hrs Serum free light chain assay: involved free light chain level =10 mg/dl (=100 mg/l) provided the serum free light chain ration is abnormal.
Patients must be accessible for treatment and follow-up procedures.
Male or female patients 18 years of age or older.
Women of childbearing potential (WOCBP) must have a negative serum pregnancy or urine pregnancy test with a sensitivity of at least 50 mIU/mL/ =7 days prior to start of treatment. Female patient is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of study drug(s), or agree to completely abstain from heterosexual intercourse.
Male patients, even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and for 3 months after the end of treatment, or completely abstain from heterosexual intercourse.
Patients must be able to understand the nature of this study and give 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 patient at anytime without prejudice to future medical care.
Previous treatment with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids (not exceeding the total equivalent of 160 mg of dexamethasone over a 2-week period) or radiation therapy will not disqualify the patient.
Patients requiring concurrent localized radiotherapy are not eligible. Two weeks must have elapsed since the date of the last radiotherapy treatment.
Patients with = National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 4.0. (NCI CTCAE v4.0) grade 2 peripheral neuropathy =14 days prior to study enrollment.
Treatment with investigational agent(s) outside of this trial, or =14 days prior to of the start of this trial and throughout the duration of subject participation.
Active infection or infection requiring intravenous antibiotic treatment at the time of accrual.
Known to be HIV positive (HIV test is not required for participation in the trial).
Patients with New York Heart Association (NYHA) (see Appendix C) class III/IV heart failure or any of the following: History of uncontrolled or symptomatic angina History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation Electrocardiographic evidence of acute ischemia or active conduction system abnormalities Myocardial infarction < 6 months from study entry Uncontrolled or symptomatic congestive heart failure Ejection fraction below the institutional normal limit Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient Uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias. Prior to study entry, any ECG abnormality at Screening must be documented by the investigator as not medically relevant.
Other serious medical conditions or psychiatric illness that would potentially interfere with patient participation in this trial.
A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least 2 years previously or low-risk prostate cancer after curative therapy.
Known hypersensitivity to bortezomib, boron, or mannitol.
Female patient is pregnant or lactating. or if applicable, had a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before the first dose of study drug. Confirmation that WOCBP are not pregnant must be established by a negative ß-human chorionic gonadotropin (ß-hCG) pregnancy test =7 days prior to start of treatment. Pregnancy testing is not required for postmenopausal or surgically sterilized women.