Clinical trial NCT00148317: Phase II Study of Velcade, Decadron, and Doxil Followed by Cyclophosphamide in Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2005-09-07
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

Brief 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).


Eligibility 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.

Primary outcomes:
measure: Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate)
timeFrame: 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
Secondary outcomes:
measure: Yield of CD34+ Stem Cells
timeFrame: Occurred after mobilization, and prior to Stem cell transplant; a 7 day limit was imposed on stem cell collection
measure: Progression Free Survival
timeFrame: Date of progression, assessed from start of trial to Final data cut off date (15 April 2011)
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Ruben Niesvizky, MD
role: PRINCIPAL_INVESTIGATOR
References: