Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

Phase II Study of VDT (VELCADE, Doxil® and Thalidomide) as Frontline Therapy for Patients With Previously Untreated Multiple Myeloma (MM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523848
• Other study ID #: CDR0000563183
• Secondary ID: RPCI-I-59105
• Status: Completed
• Phase: Phase 2
• First received: August 31, 2007
• Last updated: July 12, 2013
• Start date: June 2006
• Est. completion date: October 2012

Study information

• Verified date: July 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin hydrochloride liposome and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin hydrochloride liposome and thalidomide works as first-line therapy in treating patients with previously untreated multiple myeloma.

Description:

OBJECTIVES:

Primary

• To determine the overall response rate (complete response and partial response) in patients previously untreated stage I, II, or III multiple myeloma.

Secondary

• To evaluate the complete response rate in patients treated with this regimen.

• To determine the time to disease progression from the start of this therapy in patients treated with this regimen.

OUTLINE: Patients receive low-dose oral thalidomide once a day on days 1-28, bortezomib IV on days 1, 4, 15, and 18, and doxorubicin hydrochloride liposome IV over 60-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with residual disease who continue to show response after completion of 6 courses may receive 2 additional courses for a total of 8 courses.

After completion of study treatment, patients are followed every 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of stage I, II, or III multiple myeloma requiring therapy

• No prior systemic therapy for multiple myeloma

• Patients who have received steroids or radiotherapy for cord compression or spinal cord disease are eligible for this study

• Patients who have received 1 prior course of antimyeloma therapy may be enrolled at the investigator's discretion provided disease progression is not noted

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%

• Platelet count = 75,000 cells/mm^3 (< 75,000 cells/mm^3 secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)

• ANC = 1,000 cells/mm^3

• Hemoglobin = 8.0 g/dL (< 8 g/dL secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)

• Creatinine clearance > 20 mL/min

• AST and ALT = 2 times upper limit of normal (ULN) OR = 3 times ULN (in the presence of liver metastases)

• Alkaline phosphatase = 2 times ULN OR = 3 times ULN (in the presence of liver metastases)

• Total bilirubin = 2 times ULN OR = 3 times ULN (in the presence of liver metastases)

• Ejection fraction = 50% by MUGA or 2-D echocardiogram

• Negative pregnancy test

• Fertile patients must use at least 1 highly effective and 1 additional effective contraception method 4 weeks prior to, during, and 3 months after completion of study therapy

• HIV-negative

• Must have sufficient mental capacity to understand the explanation of the study and to provide informed consent

• Willingness and ability to comply with the FDA-mandated S.T.E.P.S. program

Exclusion criteria:

• Pregnant or lactating

• Active, serious infections uncontrolled by antibiotics

• Any medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in this clinical trial

• History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of doxorubicin hydrochloride liposome or bortezomib, boron, or mannitol

• Any of the following conditions:

• History of uncontrolled New York Heart Association class II-IV heart disease or clinical evidence of congestive heart failure

• Myocardial infarction within the past 6 months

• Uncontrolled angina

• Severe uncontrolled ventricular arrhythmias, ECG evidence of acute ischemia, or active conduction system abnormalities

• Peripheral neuropathy = grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• bortezomib
IV
• pegylated liposomal doxorubicin hydrochloride
IV
• thalidomide
Oral

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (Complete and Partial)		Every 3 months	No
Secondary	Complete Response Rate		Every 3 months	No
Secondary	Time to Disease Progression		Every 3 months	No