Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone (UPFRONT)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Millennium Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT00507416

First received: July 25, 2007

Last updated: March 28, 2014

Last verified: March 2014

History of Changes

Results First Received: March 28, 2014

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Multiple Myeloma
Interventions:	Drug: Bortezomib Drug: Dexamethasone Drug: Melphalan Drug: Prednisone Drug: Thalidomide

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 158 investigative sites in the United States from 26 June 2007 to 28 March 2013

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with previously untreated multiple myeloma were randomized in a 1:1:1 ratio to one of three treatment groups: VD: Velcade (bortezomib) and dexamethasone; VTD: Velcade, thalidomide, and dexamethasone; VMP: Velcade, melphalan, and prednisone.

Reporting Groups

	Description
Bortezomib and Dexamethasone	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Bortezomib, Thalidomide, and Dexamethasone	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Bortezomib, Melphalan and Prednisone	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).

Participant Flow: Overall Study

	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
STARTED	168	167	167
Treated (Safety Population)	165	158	163
Completed 8 Treatment Cycles	82	60	69
COMPLETED	50 ^[1]	42 ^[1]	53 ^[1]
NOT COMPLETED	118	125	114
Adverse Event	58	67	65
Protocol Violation	1	2	0
Lack ofEfficacy / Physician Decision	7	7	8
Progressive Disease	20	10	13
Patient declined further treatment	18	14	11
Other	11	16	13
Did not Receive Study Treatment	3	9	4

[1]	Completed is defined as having completed 13 treatment cycles.

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat population, defined as all participants randomized

Reporting Groups

	Description
Bortezomib and Dexamethasone	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Bortezomib, Thalidomide, and Dexamethasone	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Bortezomib, Melphalan and Prednisone	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Total	Total of all reporting groups

Baseline Measures

	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone	Total
Number of Participants [units: participants]	168	167	167	502
Age [units: years] Mean ± Standard Deviation	72.6 ± 9.35	71.3 ± 8.73	71.3 ± 8.67	71.7 ± 8.92
Age, Customized [units: participants]
≥ 65 years	140	135	139	414
≥ 75 years	84	64	62	210
≥ 80 years	40	27	23	90
Gender [units: participants]
Female	67	97	77	241
Male	101	70	90	261
Race/Ethnicity, Customized [units: participants]
White	131	124	118	373
Black	23	31	29	83
Native Hawaiian or Other Pacific Islander	0	0	2	2
Asian	2	1	0	3
American Indian or Alaskan Native	0	1	2	3
Other	10	10	15	35
Not Reported	2	0	1	3
Region of Enrollment [units: participants]
United States	168	167	167	502

Outcome Measures

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1. Primary:

Progression Free Survival (PFS) [ Time Frame: From randomization until disease progression. Median follow-up time was 43 months. ]

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2. Secondary:

Percentage of Participants With an Overall Response [ Time Frame: Response assessed every other cycle for up to 13 cycles (49 weeks). ]

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3. Secondary:

Percentage of Participants With a Complete Response [ Time Frame: Response assessed every other cycle, for up to 13 cycles (49 weeks). ]

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4. Secondary:

Percentage of Participants With a Complete Response or a Very Good Partial Response [ Time Frame: Response assessed every other cycle for up to 13 cycles (49 weeks). ]

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5. Secondary:

Duration of Response [ Time Frame: From first documented response until disease progression. Median follow-up time was 43 months. ]

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6. Secondary:

Overall Survival [ Time Frame: From randomization until death. Median follow-up time was 43 months. ]

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7. Secondary:

Time to Alternative Therapy [ Time Frame: From randomization until alternative therapy. Median follow-up time was 43 months. ]

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8. Secondary:

Change From Baseline in EORTC QLQ-C30 - Global Health Status [ Time Frame: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13 ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.

Results Point of Contact:

Name/Title: Medical Director
Organization: Millennium Pharmaceuticals Inc
phone: 1-800-778-2860
e-mail: clinicaltrialregistry@tpna.com

No publications provided

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00507416 History of Changes
Other Study ID Numbers:	C05009
Study First Received:	July 25, 2007
Results First Received:	March 28, 2014
Last Updated:	March 28, 2014
Health Authority:	United States: Food and Drug Administration

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