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

National Cancer Institute (NCI)130 sites in 1 country2 target enrollmentSeptember 2010

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 2010

End Date

March 2014

Last Updated

11 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Institute (NCI)

Responsible Party

Sponsor

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:
•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

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

Arms & Interventions

Treatment (combination chemotherapy)

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.

Intervention: liposomal doxorubicin

Treatment (combination chemotherapy)

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.

Intervention: bortezomib

Treatment (combination chemotherapy)

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.

Intervention: dexamethasone

Treatment (combination chemotherapy)

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.

Intervention: cyclophosphamide