Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant

Refractory Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01078441
• Other study ID #: NCI-2011-02002
• Secondary ID: NCI-2011-02002E2
• Status: Terminated
• Phase: Phase 2
• First received: February 27, 2010
• Last updated: January 5, 2015
• Start date: September 2010
• Est. completion date: March 2014

Study information

• Verified date: July 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma

Intervention

Drug:
• liposomal doxorubicin
Given IV
• bortezomib
Given subcutaneously.
• dexamethasone
Given orally
• cyclophosphamide
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	One-year Survival in Patients Treated With This Regimen.	Proportion of patients who are still alive at 1 year after registration.	Assessed at 1 year	No