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

NCT00148317 | Completed Phase 2 Results

• 1 other identifier: 0504007841
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

PRIMARY STUDY OBJECTIVES

• 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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate)

  Myeloma response criteria developed by Bladé et al. was used to categorize response.

  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 (2)

• Yield of CD34+ Stem Cells

  Occurred after mobilization, and prior to Stem cell transplant; a 7 day limit was imposed on stem cell collection

• Progression Free Survival

  Date of progression, assessed from start of trial to Final data cut off date (15 April 2011)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Drug: Bortezomib; Drug: dexamethasone; Drug: liposomal doxorubicin; Drug: cyclophoshamide; Drug: filgrastim

Interventions

Bortezomib DRUG

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

Also known as: velcade

Treatment Arm

dexamethasone DRUG

During Induction Phase (6 cycles): dexamethasone 40 mg on days 1-4, 8-11, and 15-18

Also known as: decadron

Treatment Arm

liposomal doxorubicin DRUG

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

Treatment Arm

cyclophoshamide DRUG

During the 21 day mobilization phase (1 cycle): cyclophosphamide at 3 g/m2 on day 8

Also known as: cytoxan

Treatment Arm

filgrastim DRUG

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

Also known as: neupogen

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; liposomal doxorubicin; Cyclophosphamide; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Jennifer Hess
• Organization: Weill Cornell Medical College

jmh2004@med.cornell.edu

6469629440

Study Officials

• Ruben Niesvizky, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 7, 2005
• Study Start: June 1, 2005
• Primary Completion: February 1, 2011
• Study Completion: November 1, 2012
• Last Updated: July 18, 2017
• Results First Posted: July 18, 2017

Record last verified: 2017-06

Locations

US (1)