Clinical trial NCT01056276: Study to Evaluate the Combination of Bendamustine, Bortezomib and Dexamethasone (BBD) in the First-Line Treatment of Patients With Multiple Myeloma Who Are Not Candidates for High Dose Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Bendamustine
Bortezomib
Dexamethasone
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
name: Cephalon
First posted: 2010-01-26
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, investigators will evaluate the activity of bendamustine, bortezomib and dexamethasone (BBD). This regimen combines 3 agents with high activity in multiple myeloma, with different mechanisms of action and non-overlapping toxicities.

Detailed description: The purpose of this study is to assess the efficacy, tolerability, and toxicity of bendamustine, bortezomib, and dexamethasone (BBD) as first-line treatment of multiple myeloma (MM) patients who are transplant ineligible or who are not candidates for high dose chemotherapy. Eligible patients will receive protocol treatment for up to 34 weeks plus the screening period (up to 2 weeks). Response assessments will occur every 4 weeks and confirmed using the International Myeloma Working Group Uniform Response Criteria. Patients having an objective response or stable disease will continue to maintenance therapy until disease progression or intolerable toxicity.

Eligibility criteria: Inclusion Criteria:

1. Patients must meet the Durie and Salmon criteria for initial diagnosis of multiple myeloma.
2. Previously histologically confirmed, multiple myeloma with indication for therapy including one of the following:

   * Hemoglobin \<10 g/dl or 2 g/dl below normal
   * Serum calcium \>11.5 mg/dl
   * Creatinine \>2 mg/dl
   * Lytic bone lesions or severe osteopenia
   * Extramedullary plasmacytomas
3. 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.
4. ECOG Performance Status 0-2.
5. WBC ≥3000/mL; ANC ≥1000/mL; platelets ≥50,000/mL (patients with platelets ≥30,000/mL are eligible if thrombocytopenia is felt to be due to extensive bone marrow involvement with myeloma).
6. 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).
7. Patients must have measurable or evaluable disease. In patients with disease limited to bone and bone marrow, serial paraprotein measurements are acceptable for evaluable disease.
8. Patients must be accessible for treatment and follow-up procedures.
9. Male or female patients 18 years of age or older.
10. Patients must provide written informed consent prior to receiving protocol therapy.
11. Women of childbearing potential must agree to use a medically acceptable method of birth control(e.g., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 12 months after their last dose of rituximab. Men must use an acceptable form/method of contraception for the duration of treatment and for 3 months after the end of treatment.
12. Patients must be able to understand the nature of this study and give written informed consent.

Exclusion Criteria:

1. Previous therapy for multiple myeloma with the exception of an initial 4-day course of pulsed dexamethasone.
2. Patients with ≥NCI CTCAE v4.0 grade 2 peripheral neuropathy ≤14 days prior to study enrollment.
3. Treatment with investigational agent(s) ≤14 days prior to study enrollment.
4. Active infection or infection requiring intravenous antibiotic treatment at the time of accrual.
5. Known to be HIV positive (HIV test is not required for participation in the trial).
6. Patients with class III/IV cardiac problems as defined by the New York Heart Association (NYHA)criteria:

   * History of uncontrolled or symptomatic angina
   * History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
   * 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.
7. Other serious medical conditions or psychiatric illness that would potentially interfere with patient participation in this trial.
8. 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.
9. Known hypersensitivity to bortezomib, boron, or mannitol.
10. Female patient is pregnant or lactating. Confirmation that female patients of childbearing potential are not pregnant must be established by a negative serum pregnancy test ≤7 days prior to start of treatment.

Primary outcomes:
measure: Complete Response Rate
timeFrame: every 8 weeks for approximately 48 months
measure: Number of Patients Who Experienced Serious and Non-serious Adverse Events
timeFrame: approximately 36 weeks
Secondary outcomes:
measure: Progression Free Survival
timeFrame: every 8 weeks for up to 48 months
measure: Overall Survival
timeFrame: every 4 weeks until progressive disease then every 12 weeks, projected 48 months
measure: Overall Response Rate
timeFrame: every 4 weeks for approximately 2 years
Other outcomes:
Locations:
city: Thousand Oaks
country: United States
facility: Los Robles Hospital and Medical Center
state: California
city: Ft. Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic, LLP
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Bethesda
country: United States
facility: National Capital Clinical Research Consortium
state: Maryland
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc.
state: Ohio
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Arlington
country: United States
facility: Leading Edge Research, PA
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Jesus Berdeja, M.D.
role: STUDY_CHAIR
References: