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

NCT ID: NCT01056276

Last Updated: 2017-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2017-02-28

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Bendamustine, Bortezomib,and Dexamethasone for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by IMWG criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone until disease progression or intolerable toxicity.

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

Treatment: 80 mg/m2 via intravenous (IV) Days 1 and 2; repeat cycles every 28-days for 8 cycles or 2 cycles beyond confirmed complete response.

Bortezomib

Intervention Type: DRUG

1.3 mg/m2 IV Days 1, 8, 15; repeat cycles every 28-days for 8 cycles or 2 cycles beyond confirmed complete response.

Maintenance: 1.3 mg/m2 IV or SQ Days 1, 15

Dexamethasone

Intervention Type: DRUG

20 mg orally (PO) Days 1, 2, 8, 9, 15, 16 every 28-days for 8 cycles or 2 cycles beyond confirmed complete response, Maintenance: 20 mg PO Days 1, 15

Interventions

Bendamustine

Treatment: 80 mg/m2 via intravenous (IV) Days 1 and 2; repeat cycles every 28-days for 8 cycles or 2 cycles beyond confirmed complete response.

Intervention Type: DRUG

Bortezomib

1.3 mg/m2 IV Days 1, 8, 15; repeat cycles every 28-days for 8 cycles or 2 cycles beyond confirmed complete response.

Maintenance: 1.3 mg/m2 IV or SQ Days 1, 15

Intervention Type: DRUG

Dexamethasone

20 mg orally (PO) Days 1, 2, 8, 9, 15, 16 every 28-days for 8 cycles or 2 cycles beyond confirmed complete response, Maintenance: 20 mg PO Days 1, 15

Intervention Type: DRUG

Other Intervention Names

Treanda; Velcade

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Cephalon

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesus Berdeja, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Los Robles Hospital and Medical Center

Thousand Oaks, California, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Hematology Oncology Clinic, LLP

Baton Rouge, Louisiana, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

National Capital Clinical Research Consortium

Bethesda, Maryland, United States

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Oncology Hematology Care Inc.

Cincinnati, Ohio, United States

South Carolina Oncology Associates

Columbia, South Carolina, United States

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

Leading Edge Research, PA

Arlington, Texas, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Peninsula Cancer Institute

Newport News, Virginia, United States

Countries

United States

Other Identifiers

SCRI MM 23

Identifier Type: -

Identifier Source: org_study_id