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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01056276
• Other study ID #: SCRI MM 23
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 22, 2010
• Last updated: July 28, 2016
• Start date: May 2010
• Est. completion date: April 2017

Study information

• Verified date: July 2016
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

In this study, the 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: April 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bendamustine
80 mg/m2 IV Days 1 and 4; repeat cycles every 28-days
• Bortezomib
1.3 mg/m2 IV Days 1, 4, 8, 11; repeat cycles every 28-days
• Dexamethasone
40 mg PO Days 1, 2, 3, 4; repeat cycles every 28-days

Locations

Country	Name	City	State
United States	Leading Edge Research, PA	Arlington	Texas
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	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Oncology Hematology Care Inc.	Cincinnati	Ohio
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Florida Cancer Specialists	Ft. Myers	Florida
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Tennessee Oncology	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Los Robles Hospital and Medical Center	Thousand Oaks	California

Sponsors (3)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Cephalon, Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR) rate as measure of efficacy	Efficacy of the Bendamustine-Bortezomib-Dexamethasone (BBD) combination will be assessed using the International Myeloma Working group Uniform Response Criteria. Defined as an observed CR rate of 25%.	24 months	No
Primary	Number of treatment-emergent toxicities as a measure of safety and tolerability.	Assessed using NCI CTCAE v4.0	every cycle (4 weeks) until disease progression or intolerable toxicity occurs, up to 34 weeks	Yes
Secondary	Progression Free Survival	Defined as the date of first protocol treatment to date of documented tumor progression or date of death.	every 4 weeks, projected 24 months	No
Secondary	Overall Survival	Defined as the interval from the first study treatment until the date of death	Every 4 weeks until disease progression or death, projected 24 months	No
Secondary	Overall Response Rate	Defined as the proportion of patients with observed complete response (CR) or partial response (PR).	every 4 weeks until treatment discontinuation, projected 24 months	No