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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00148317
First Posted: September 7, 2005
Last Update Posted: July 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Weill Medical College of Cornell University
  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 Drug: dexamethasone Drug: liposomal doxorubicin Drug: cyclophoshamide Drug: filgrastim Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:

Consolidation: All patients will receive 2 cycles of bortezomib (VEL) and dexamethasone (DEX). Patients who achieve a complete response after 2 cycles will receive 4 additional cycles of VEL/DEX before mobilization.

Patients who do not achieve at least a partial response after 2 cycles will receive 4 more cycles of VEL/DEX plus DOXIL.

Patients who achieve a partial response after 2 cycles on VEL/DEX, will continue this combination for 2 more cycles. Patients who achieve a complete response after 4 cycles will receive 2 additional cycles of VEL/DEX before mobilization. Patients who remain with a partial response after 4 cycles of VEL/DEX will receive 2 additional cycles of the combination of VEL/DEX plus DOXIL.

Mobilization: Patients who complete 6 cycles of consolidation will proceed to mobilization. Patients will receive one cycle of VEL plus high dose CYTOXAN followed by G-CSF beginning 24 hours after CYTOXAN given for a total of 10 daily doses.

Masking: None (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 (Overall Response Rate) [ Time Frame: Best response at any point during each respective study phase was collected - once after consolidation/prior to mobilization (approximately 6 cycles after start of treatment), and once after mobilization ]
    Myeloma response criteria developed by Bladé et al. was used to categorize response.


Secondary Outcome Measures:
  • Yield of CD34+ Stem Cells [ Time Frame: Occurred after mobilization, and prior to Stem cell transplant; a 7 day limit was imposed on stem cell collection ]
    This is the yield of CD34+ stem cells collection after high dose cyclophosphamide.

  • Progression Free Survival [ Time Frame: Date of progression, assessed from start of trial to Final data cut off date (15 April 2011) ]

    Response was assessed using IMWG guidelines, which for progressive disease are as follows:

    Increase of > 25% from lowest response value in any one or more of the following:

    • Serum M-component and/or (the absolute increase must be > 0.5 g/dL)*
    • Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
    • Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL
    • Bone marrow plasma cell percentage; the absolute percentage must be > 10%
    • Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
    • Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder IF starting M protein component is > 5g/dL, then absolute increase of 1g is sufficient for progression.


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
During Induction Phase (6 cycles): Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 During 21-day mobilization cycle (1 cycle): Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11
Other Name: velcade
Drug: dexamethasone
During Induction Phase (6 cycles): dexamethasone 40 mg on days 1-4, 8-11, and 15-18
Other Name: decadron
Drug: liposomal doxorubicin
If patients achieve less then a PR during the induction phase after 2 cycles, or less then a CR after 4 cycles: Liposomal doxorubicin was added at 30 mg/m2 on day 4 for the remaining cycles
Drug: cyclophoshamide
During the 21 day mobilization phase (1 cycle): cyclophosphamide at 3 g/m2 on day 8
Other Name: cytoxan
Drug: filgrastim
During the 21 day mobilization phase (1 cycle): 10 μg/kg/day for 10 consecutive days starting 24 hours after cyclophosphamide administration on day 9
Other Name: neupogen

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00148317     History of Changes
Other Study ID Numbers: 0504007841
First Submitted: September 2, 2005
First Posted: September 7, 2005
Results First Submitted: February 24, 2017
Results First Posted: July 18, 2017
Last Update Posted: July 18, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Liposomal doxorubicin
Cyclophosphamide
Doxorubicin
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists