Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant
- Conditions
- Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT01078441
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial is studying how well giving bortezomib together with liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide works in treating patients with multiple myeloma that relapsed after autologous stem cell transplant. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide may kill more cancer cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the 1-year survival of patients with relapsed multiple myeloma treated with bortezomib, liposomal doxorubicin, dexamethasone, and cyclophosphamide.
SECONDARY OBJECTIVES:
I. To evaluate response rates in patients treated with this regimen.
II. To evaluate the median time to progression in patients treated with this regimen.
III. To evaluate the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Peripheral blood and bone marrow samples may be collected for future research. Patients complete the Functional Assessment of Cancer Therapy (FACT) neurotoxicity questionnaire periodically.
After completion of study treatment, patients are followed up every 3 months for 3 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
-
Diagnosis of multiple myeloma that was symptomatic at the time of initial diagnosis
-
Must have met the following criteria at one point during the disease course:
-
Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy-proven plasmacytoma
-
Symptomatic disease at initial diagnosis that prompted the initiation of therapy as well as evidence of end-organ damage at the time of diagnosis, including at least 1 of the following:
- Anemia
- Hypercalcemia
- Bone disease (lytic bone lesions or pathologic fracture)
- Renal dysfunction
-
-
Disease relapsed < 12 months after autologous stem cell transplantation (SCT)
-
Measurable disease, as defined by the presence of ≥ 1 of the following:
- Serum M-spike ≥ 1 g/dL
- Urine M-spike ≥ 200 mg/24 hours
- Involved free light chain (FLC) ≥ 10 mg/dL (provided the serum FLC is abnormal)
- Plasma cells ≥ 30%
-
ECOG performance status 0-2
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
At least 14 days since prior palliative and/or localized radiotherapy
-
Left ventricular ejection fraction (LVEF) normal by Echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan
-
Hemoglobin > 8 g/dL
-
Platelet count ≥ 75,000/mm^3 (without transfusion support)
-
Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (without use of growth factors)
-
Creatinine < 2.5 mg/dL
-
Direct bilirubin ≤ 1.5 mg/dL
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal
-
All tests below must be performed within 14 days prior to registration:
- Serum free light chain assay
- Kappa free light chain
- Lambda free light chain
-
Prior malignancy allowed provided it was treated curatively and has not relapsed in 5 years
- Patients with basal cell skin cancer, in situ cervical cancer, or prostate cancer not requiring therapy are eligible
-
Therapy for relapsed disease following SCT
-
Known allergy to bortezomib or anthracyclines
-
Prior allogeneic SCT
-
Peripheral neuropathy ≥ grade 2 according to the Cancer Therapy Evaluation Program (CTEP) active version of the NCI Common Terminology Criteria for Adverse Events (CTCAE)
-
Concurrent uncontrolled illness that would limit study compliance, including the following:
- Uncontrolled hypertension
- Symptomatic congestive heart failure
- Unstable angina
- Uncontrolled cardiac arrhythmia
- Uncontrolled psychiatric illness or social situation
- Active uncontrolled infection
-
Prior doxorubicin hydrochloride exposure > 240 mg/m^2
-
Active, uncontrolled seizure disorder
-
Seizures within the past 6 months
-
Pregnant or nursing
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (combination chemotherapy) liposomal doxorubicin Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) bortezomib Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) cyclophosphamide Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) dexamethasone Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method One-year Survival in Patients Treated With This Regimen. Assessed at 1 year Proportion of patients who are still alive at 1 year after registration.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (130)
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸Grand Junction, Colorado, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Saint Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Littleton Adventist Hospital
🇺🇸Littleton, Colorado, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
Parker Adventist Hospital
🇺🇸Parker, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Exempla Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Medical Center of Central Georgia
🇺🇸Macon, Georgia, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸Galesburg, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸Peoria, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸Clive, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸Des Moines, Iowa, United States
Iowa Oncology Research Association CCOP
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - North Iowa
🇺🇸Mason City, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Siouxland Hematology Oncology Associates
🇺🇸Sioux City, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸Sioux City, Iowa, United States
Saint Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas - McPherson
🇺🇸McPherson, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸Wichita, Kansas, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Wichita CCOP
🇺🇸Wichita, Kansas, United States
Union Hospital of Cecil County
🇺🇸Elkton MD, Maryland, United States
Bixby Medical Center
🇺🇸Adrian, Michigan, United States
Hickman Cancer Center
🇺🇸Adrian, Michigan, United States
Community Cancer Center of Monroe
🇺🇸Monroe, Michigan, United States
Mercy Memorial Hospital
🇺🇸Monroe, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview-Southdale Hospital
🇺🇸Edina, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Metro-Minnesota CCOP
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Toledo Clinic Cancer Centers-Bowling Green
🇺🇸Bowling Green, Ohio, United States
Hematology Oncology Center Incorporated
🇺🇸Elyria, Ohio, United States
Community Health Partners Regional Medical Center
🇺🇸Elyria, Ohio, United States
North Coast Cancer Care-Clyde
🇺🇸Clyde, Ohio, United States
Lima Memorial Hospital
🇺🇸Lima, Ohio, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸Maumee, Ohio, United States
Fisher-Titus Medical Center
🇺🇸Norwalk, Ohio, United States
Saint Charles Hospital
🇺🇸Oregon, Ohio, United States
Toledo Clinic Cancer Centers-Oregon
🇺🇸Oregon, Ohio, United States
North Coast Cancer Care
🇺🇸Sandusky, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸Tiffin, Ohio, United States
Flower Hospital
🇺🇸Sylvania, Ohio, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Toledo Community Hospital Oncology Program CCOP
🇺🇸Toledo, Ohio, United States
Saint Vincent Mercy Medical Center
🇺🇸Toledo, Ohio, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Mercy Saint Anne Hospital
🇺🇸Toledo, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸Toledo, Ohio, United States
Fulton County Health Center
🇺🇸Wauseon, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Geisinger Medical Center-Cancer Center Hazelton
🇺🇸Hazleton, Pennsylvania, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Geisinger Wyoming Valley
🇺🇸Wilkes-Barre, Pennsylvania, United States
Fredericksburg Oncology Inc
🇺🇸Fredericksburg, Virginia, United States
UW Cancer Center Johnson Creek
🇺🇸Johnson Creek, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Eastern Cooperative Oncology Group
🇺🇸Boston, Massachusetts, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
The Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Butler Memorial Hospital
🇺🇸Butler, Pennsylvania, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Exempla Saint Joseph Hospital
🇺🇸Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸Denver, Colorado, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States