Combination Bortezomib-Containing Regimens in Newly Diagnosed Patients With t (4; 14) Positive Multiple Myeloma - Full Text View

Sponsors and Collaborators:	University Health Network, Toronto Princess Margaret Hospital, Canada Ortho Biotech, Inc.
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00570180

Purpose

Given the disappointing results with routine ASCT in t(4;14) patients, we propose this open label phase II study of bortezomib along with dexamethasone and pegylated liposomal doxorubicin (Doxil/Caelyx), referred to as the DBd regimen, for 4 cycles, followed by post-induction therapy with cyclophosphamide + bortezomib + prednisone (referred to as the CyBorP regimen) for 8 cycles. Since patients with t(4;14) remain at high risk for relapse, maintenance therapy with dexamethasone for 4 days each month will be given until disease progression.

Condition	Intervention	Phase
Multiple Myeloma	Drug: Bortezomib	Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Prednisone Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	An Open-Label Phase II Study of the Efficacy of Combination Bortezomib-Containing Regimens in the Treatment of Newly Diagnosed Patients With t (4; 14) Positive Multiple Myeloma

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

To determine the time to progression (TTP) with this treatment regimen [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the objective response rate/duration following DBd induction and Cybor P post induction therapy [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
To determine PFS [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
To determine overall survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
To determine the safety profile of this regimen [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	45
Study Start Date:	November 2007
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Single Arm: Experimental Please see intervention description	Drug: Bortezomib 21 day-cycle Induction therapy:bortezomib 1.3 mg/m2 (I.V. bolus on Days 1, 4, 8, and 11), then 10-day rest period (Days 12 to 21). DOXIL 30 mg/m2 given after bortezomib (1-hour I.V. infusion on Day 4 of each 21-day cycle). Dexamethasone 40 mg PO on days 1-4,8-11 and 15-18 during the first cycle. Subsequent 3 cycles, dexamethasone 40 mg PO given on days 1-4 and 11-14. Patients who don't progress may undergo elective stem cell mobilization, stem cell collection and cryopreservation. Patients will then receive post-induction therapy 1.5 mg/m2 bortezomib days 1, 8, and 15 I.V. + cyclophosphamide 300 mg/m2 PO weekly + prednisone 100 mg PO on alternate days for 8 monthly 28 day cycles.Maintenance therapy with 4 days of 40 mg dexamethasone (days 1-4) per month until disease progression occurs.

Arms

Assigned Interventions

Single Arm: Experimental

Please see intervention description

Drug: Bortezomib

21 day-cycle Induction therapy:bortezomib 1.3 mg/m2 (I.V. bolus on Days 1, 4, 8, and 11), then 10-day rest period (Days 12 to 21). DOXIL 30 mg/m2 given after bortezomib (1-hour I.V. infusion on Day 4 of each 21-day cycle). Dexamethasone 40 mg PO on days 1-4,8-11 and 15-18 during the first cycle. Subsequent 3 cycles, dexamethasone 40 mg PO given on days 1-4 and 11-14. Patients who don't progress may undergo elective stem cell mobilization, stem cell collection and cryopreservation. Patients will then receive post-induction therapy 1.5 mg/m2 bortezomib days 1, 8, and 15 I.V. + cyclophosphamide 300 mg/m2 PO weekly + prednisone 100 mg PO on alternate days for 8 monthly 28 day cycles.Maintenance therapy with 4 days of 40 mg dexamethasone (days 1-4) per month until disease progression occurs.

Show Detailed Description

Eligibility

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

Criteria

Inclusion Criteria:

Patients previously diagnosed with MM based on criteria from the International Myeloma Working Group (IMWG)
Patients who have 'measurable' disease
Age 18 years at the time of signing Informed Consent
Patients must not have received prior chemotherapy for multiple myeloma, although up to 160 mg of dexamethasone is allowed after discussion with the P.I
Patient is t(4;14) positive on screening assay.

Exclusion Criteria:

Concomitant therapy medications that include corticosteroids (> 10 mg per day of prednisone or equivalent) or other therapy that is or may be active against myeloma or therapy with radiation within 3 weeks prior to day 1. Patients must not have received prior chemotherapy for multiple myeloma, although up to 480 mg of dexamethasone is allowed after discussion with the P.I. while waiting for the results of cytogenetic testing in patients requiring urgent initiation of anti-myeloma therapy.
Peripheral neuropathy of Grade 2 or greater.
Patients with evidence of mucosal or internal bleeding and/or refractoriness to platelet transfusions (i.e., unable to maintain a platelet count 50 x 109 /L).
renal failure requiring dialysis or patient with a serum creatinine level > 309 umol/L
Pregnant or lactating women

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570180

Contacts

Contact: Jesus G. Piza, MD, CCRP	416-946-4627	Jesus.PizaRogriguez@uhn.on.ca
Contact: Mariela Pantoja, PhD, CCRP	416-946-4501 ext 3655	Mariela.Pantoja@uhn.on.ca

Locations

Canada, Alberta
Tom Baker Cancer Centre	Not yet recruiting
Calgary, Alberta, Canada, T2N 2T9
Principal Investigator: Nizar Bahlis, MD
Cross Cancer Institute 11560 University Ave	Not yet recruiting
Edmonton, Alberta, Canada, T6G-1Z2
Principal Investigator: Andrew Belch, MD
Canada, Manitoba
CancerCare Manitoba 675 McDermot Ave.	Not yet recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Principal Investigator: David Szwajcer, MD
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre.	Not yet recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Principal Investigator: Darrell White, MD
Canada, Ontario
London Regional Cancer Program 790 Commissioners Road East	Not yet recruiting
London, Ontario, Canada, N6A 4L6
Principal Investigator: Michael Kovacs, MD
The Ottawa Hospital	Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L6
Principal Investigator: Harold Atkins, MD
Juravinski Cancer Centre 699 Concession Street	Not yet recruiting
Hamilton, Ontario, Canada, L8V 5C2
Principal Investigator: Deborah Marcellus, MD
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Principal Investigator: Donna E Reece, MD
Canada, Saskatchewan
Saskatoon Cancer Centre 20 Campus Drive	Not yet recruiting
Saskatoon, Saskatchewan, Canada, S7N 4H4
Principal Investigator: Michael Voralia, MD

Sponsors and Collaborators

University Health Network, Toronto

Princess Margaret Hospital, Canada

Ortho Biotech, Inc.

Investigators

Principal Investigator:

Donna E. Reece, MD

University Health Network, Princess Margaret Hospital

More Information

Responsible Party:	University Health Network, Princess Margaret Hospital ( Donna Reece, MD/ Multiple Myeloma Program Director )
Study ID Numbers:	26866138-MMY-2016, t4;14 trial PMH
Study First Received:	December 6, 2007
Last Updated:	June 3, 2008
ClinicalTrials.gov Identifier:	NCT00570180
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:

newly diagnosed

Study placed in the following topic categories:

Dexamethasone
Prednisone
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Vascular Diseases
Paraproteinemias

Cyclophosphamide
Hemostatic Disorders
Doxorubicin
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Dexamethasone acetate
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Cardiovascular Diseases
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 13, 2009