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

NCT01056276 | Completed Phase 2 Results

• 1 other identifier: SCRI MM 23
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 13

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Bendamustine; Bortezomib; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate

  Defined as the percent of patients having a complete response (CR) to treatment, assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. CR=disappearance of soft tissue plasmacytomas and 5% or less plasma cells in bone marrow.

  every 8 weeks for approximately 48 months

• Number of Patients Who Experienced Serious and Non-serious Adverse Events

  All serious adverse events (SAEs) and non-serious adverse events (AEs) were assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0, and were collected from start of study treatment until 30 days after last dose of study medication. Refer to the Adverse Event module for specific terms.

  approximately 36 weeks

Secondary Outcomes (3)

• Progression Free Survival

  every 8 weeks for up to 48 months

• Overall Survival

  every 4 weeks until progressive disease then every 12 weeks, projected 48 months

• Overall Response Rate

  every 4 weeks for approximately 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: Bendamustine; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Bendamustine 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.

Also known as: Treanda

Treatment

Bortezomib 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

Also known as: Velcade

Treatment

Dexamethasone 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

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the Durie and Salmon criteria for initial diagnosis of multiple myeloma.
• 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
• 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.
• 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).
• 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 or evaluable disease. In patients with disease limited to bone and bone marrow, serial paraprotein measurements are acceptable for evaluable disease.
• Patients must be accessible for treatment and follow-up procedures.

You may not qualify if:

• Previous therapy for multiple myeloma with the exception of an initial 4-day course of pulsed dexamethasone.
• Patients with ≥NCI CTCAE v4.0 grade 2 peripheral neuropathy ≤14 days prior to study enrollment.
• Treatment with investigational agent(s) ≤14 days prior to study enrollment.
• 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 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.
• Other serious medical conditions or psychiatric illness that would potentially interfere with patient participation in this trial.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Cephalon: collaborator

Study Sites (13)

Los Robles Hospital and Medical Center

Thousand Oaks, California, 91360, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Hematology Oncology Clinic, LLP

Baton Rouge, Louisiana, 70809, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

National Capital Clinical Research Consortium

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

Oncology Hematology Care Inc.

Cincinnati, Ohio, 45242, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Leading Edge Research, PA

Arlington, Texas, 75213, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Charles Davis, RAC
• Organization: Sarah Cannon Development Innovations

charles.davis2@scri-innovations.com

Study Officials

• Jesus Berdeja, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2010
• First Posted: January 26, 2010
• Study Start: May 1, 2010
• Primary Completion: August 1, 2015
• Study Completion: February 1, 2017
• Last Updated: May 3, 2017
• Results First Posted: March 28, 2017

Record last verified: 2017-03

Locations

US (13)