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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: bortezomib; Drug: thalidomide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 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	Drug: pegylated liposomal doxorubicin hydrochloride; IV; Drug: bortezomib; IV; Drug: thalidomide; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (Complete and Partial)	Every 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Complete Response Rate	Every 3 months
Time to Disease Progression	Every 3 monthsntil the date of first documented progression or date of death from any cause, whichever came first

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Kelvin Lee, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 31, 2007
• First Submitted That Met QC Criteria: August 31, 2007
• First Posted (Estimate): September 3, 2007

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antibiotics, Antineoplastic; Thalidomide; Bortezomib; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CDR0000563183; RPCI-I-59105 (Other Identifier: Roswell Park Cancer Institute)