Phase II Study of Velcade, Decadron, and Doxil Followed by Cyclophosphamide in Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Sequential Phase II Trial of the Combination of Bortezomib (VELCADE), Dexamethasone (DECADRON) and Pegylated Liposomal Doxorubicin (DOXIL) Followed by High Dose Cyclophosphamide in Multiple Myeloma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00148317
• Other study ID #: 0504007841
• Status: Completed
• Phase: Phase 2
• First received: September 2, 2005
• Last updated: November 20, 2012
• Start date: June 2005
• Est. completion date: November 2012

Study information

• Verified date: November 2012
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

PRIMARY STUDY OBJECTIVES

• To evaluate the efficacy of the combination of bortezomib, dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as a therapy for two different subsets of multiple myeloma patients:

1. Patients post first line therapy

2. Patients with relapsed/refractory disease who are bortezomib-naïve

• To evaluate the safety of the combination of bortezomib and dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as therapy for patients with multiple myeloma.

SECONDARY STUDY OBJECTIVES

• To evaluate the role of the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide on the ability to collect > 10 x 106 CD34+ cells/kg in < 7 collections (for both subsets of multiple myeloma patients).

• To evaluate the survival of patients who receive the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide (for both subsets of patients).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: November 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject must voluntarily sign and understand written informed consent.

• Confirmed diagnosis of multiple myeloma as specified by the SWOG criteria and is detailed in Appendix I.

• Measurable disease as defined the following:

1. For patients post induction therapy, any measurable paraprotein in the serum or urine and/or any plasmacytoma present on physical exam or imaging.

2. For patients with relapsed/refractory disease, > 0.5 g/dL serum monoclonal protein, > 0.1 g/dL serum free light chains, > 0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).

• Age > or = than 18 years at the time of signing the informed consent form.

• Karnofsky performance status> or =70% (>60% if due to bony involvement of myeloma).

• Group A (post-induction therapy)- patients who have received only one prior treatment regimen (eg VAD, Thal/Dex, BLT-D, MP, BiRD, or DVd) with at least 20 patients having received a Revlimid based regimen or Group B(>1st line of therapy)- patients with relapsed/refractory multiple myeloma who have received two or more prior treatment regimens .

• If the patient is a woman of childbearing age, she must have a negative serum or urine pregnancy test within 7 days of starting study and must use effective contraception throughout the course of the study.

• Life expectancy > 12 weeks.

• Absolute neutrophil count (ANC)> or = 1500 cells/mm3 (> or = 1000 for patients with bone marrow biopsy displaying > 50% involvement by myeloma)

• Platelets count > or = 50,000/mm3 (> or = 30,000 for patients with bone marrow biopsy displaying > 50% involvement by myeloma)

• Hemoglobin > 9.0 g/dL

• Serum SGOT/AST <3.0 x upper limits of normal (ULN)

• Serum SGPT/ALT <3.0 x upper limits of normal (ULN)

• Serum creatinine < 2.5 mg/dL or creatinine clearance > 40ml/min

• Serum total bilirubin < 1.5 x ULN

• Patients must have a MUGA scan with LVEF >50%

Exclusion Criteria:

• Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.

• Prior treatment with bortezomib.

• Peripheral neuropathy of > Grade 2 as defined by CTCAE Version 3.0 (see Appendix II)

• History of allergic reactions to compounds containing mannitol, bortezomib, conventional formulation of doxorubicin HCL or the components of DOXIL.

• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years.

• NYHA Class III or IV heart disease. History of active unstable angina, congestive heart disease, serious uncontrolled cardiac arrhythmia or myocardial infarction within 6 months.

• Female patients who are pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

• Known HIV or hepatitis A, B, or C positivity

• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.

• Any concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis).

• No prior anti-myeloma therapy within 2 weeks of treatment initiation.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin, Cyclophosphamide
Bortezomib 1.3 mg/m2 days 1, 4, 8, 11 (initial cycles) Dexamethasone 40 mg Days 1-4, 8-11, 15-18 (initial cycles) Doxil 30 mg/m2 Day 4 of subsequent cycles

Locations

Country	Name	City	State
United States	Weill Medical College of Cornell University	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	efficacy of drug combination as therapy for myeloma		duration of study	No

External Links

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