Clinical trial NCT01078441: Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant
Official title: A Phase II Study of Bortezomib, Liposomal Doxorubicin, Dexamethasone, and Cyclophosphamide in Patients With Multiple Myeloma Relapsing Within 12 Months of Autologous Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Refractory Multiple Myeloma
Keywords: Bortezomib
Liposomal Doxorubicin
Dexamethasone
Cyclophosphamide
refractory multiple myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-03-02
Enrollment: 2
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: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: One-year Survival in Patients Treated With This Regimen.
timeFrame: Assessed at 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Aurora
country: United States
facility: The Medical Center of Aurora
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Exempla Saint Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: Colorado Cancer Research Program CCOP
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: Saint Mary's Hospital and Regional Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Lakewood
country: United States
facility: Saint Anthony Hospital
state: Colorado
city: Littleton
country: United States
facility: Littleton Adventist Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Parker
country: United States
facility: Parker Adventist Hospital
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Macon
country: United States
facility: Medical Center of Central Georgia
state: Georgia
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare Galesburg
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Cancer Treatment Center
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association CCOP
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Laurel
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Mason City
country: United States
facility: Mercy Medical Center - North Iowa
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas-Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas-Liberal
state: Kansas
city: McPherson
country: United States
facility: Cancer Center of Kansas - McPherson
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Main Office
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Elkton MD
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Eastern Cooperative Oncology Group
state: Massachusetts
city: Adrian
country: United States
facility: Bixby Medical Center
state: Michigan
city: Adrian
country: United States
facility: Hickman Cancer Center
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview-Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: New Ulm
country: United States
facility: New Ulm Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota CCOP
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology and Hematology PA-Woodbury
state: Minnesota
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Bowling Green
country: United States
facility: Toledo Clinic Cancer Centers-Bowling Green
state: Ohio
city: Cincinnati
country: United States
facility: The Jewish Hospital
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Clyde
country: United States
facility: North Coast Cancer Care-Clyde
state: Ohio
city: Elyria
country: United States
facility: Community Health Partners Regional Medical Center
state: Ohio
city: Elyria
country: United States
facility: Hematology Oncology Center Incorporated
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Toledo Clinic Cancer Centers-Maumee
state: Ohio
city: Norwalk
country: United States
facility: Fisher-Titus Medical Center
state: Ohio
city: Oregon
country: United States
facility: Saint Charles Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic Cancer Centers-Oregon
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Saint Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Toledo
country: United States
facility: Toledo Community Hospital Oncology Program CCOP
state: Ohio
city: Toledo
country: United States
facility: Mercy Saint Anne Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers-Toledo
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Butler
country: United States
facility: Butler Memorial Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Medical Center-Cancer Center Hazelton
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley
state: Pennsylvania
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology Inc
state: Virginia
city: Johnson Creek
country: United States
facility: UW Cancer Center Johnson Creek
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Shaji Kumar, M.D.
role: STUDY_CHAIR
References: