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

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00148317
First received: September 2, 2005
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

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).

Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin, Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • efficacy of drug combination as therapy for myeloma [ Time Frame: duration of study ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: June 2005
Study Completion Date: November 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00148317

Locations
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Ruben Niesvizky, MD Weill Medical College of Cornell University
  More Information

Additional Information:
No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00148317     History of Changes
Other Study ID Numbers: 0504007841
Study First Received: September 2, 2005
Last Updated: November 20, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Liposomal doxorubicin
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 23, 2014