A Study of Thalidomide Plus Dexamethasone (Thal-Dex) Versus DOXIL plusThalidomide Plus Dexamethasone (DOXIL -Thal-Dex) in Patients With Newly Diagnosed Multiple Myeloma

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00097981
• Collaborator: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA (Industry)
• Enrollment: 225
• Locations: 58
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if Thalidomide + Dexamethasone or DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone is more effective in treating newly diagnosed patients with multiple myeloma. The number of patients whose multiple myeloma disappears for a period of time (complete Response) will be studied to make the determination of which treatment is more effective.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Thalidomide; Drug: Dexamethasone; Drug: DOXIL	Phase 3

Detailed Description

This is a multi-center, open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance) study to compare the safety and effectiveness of Thalidomide + Dexamethasone versus DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone in patients with newly diagnosed multiple myeloma. Treatments are administered in 28-day cycles. Patients will receive 4 to 12 treatment cycles, depending on the response of their multiple myeloma to the treatment (measured according to the European Group for Blood and Marrow Transplant Response Criteria). Patients will have additional tests that include Multiple Gated Acquisition (MUGA) scans or echocardiograms to assess the patients for potential cardiotoxicity that could be related to treatment with DOXIL (doxorubicin HCl liposome injection). Maximum duration of study participation for each participant will be 48 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Multi-Center Trial Comparing Thalidomide Plus Dexamethasone (Thal-Dex) Versus DOXIL plusThalidomide Plus Dexamethasone (DOXIL -Thal-Dex) in Subjects With Newly Diagnosed Multiple Myeloma
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Thalidomide + dexamethasone	Drug: Thalidomide; Participants will receive thalidomide orally every night (at bedtime) without food on days 1-28 and dosing will gradually increase during Cycle 1 starting at 50 mg on 1 to 7 days, 100 mg on 8 to 14 days, 150 mg on 15 to 21 days, and 200 mg 22 to 28 days. Thalidomide 200 mg per day will be administered for subsequent cycles. Participants will receive thalidomide for minimum of 4 cycles and a maximum of 12 cycles.; Drug: Dexamethasone; Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.
Experimental: Thalidomide + dexamethasone + DOXIL	Drug: Thalidomide; Participants will receive thalidomide orally every night (at bedtime) without food on days 1-28 and dosing will gradually increase during Cycle 1 starting at 50 mg on 1 to 7 days, 100 mg on 8 to 14 days, 150 mg on 15 to 21 days, and 200 mg 22 to 28 days. Thalidomide 200 mg per day will be administered for subsequent cycles. Participants will receive thalidomide for minimum of 4 cycles and a maximum of 12 cycles.; Drug: Dexamethasone; Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.; Drug: DOXIL; DOXIL 40 mg/m2 will be administered iintravenously (into a vein) on Day 1.

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate: Number of Participants Who Achieved a Complete Response [From Cycle 2 until 28 days following completion of treatment]

   Complete response rate to study medication is defined as number of participants who acheived complete response by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions. Complete response was assessed at the beginning of every treatment cycle prior to treatment, starting at Cycle 2.

Secondary Outcome Measures

1. Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) [From Cycle 2 until 28 days following completion of treatment]

   Overall response to study medication is defined as number of participants who acheived a complete response (CR) or partial response (PR) by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.

2. Time to 1st Response [From Cycle 2 until 28 days following completion of treatment]

   Time to first response was defined as the interval from date of randomization to date of achieving a partial response (PR) or better according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.

3. Time to Progression [From randomization until death or as assessed up to 2 years post last participant last treatment visit]

   Time to progression is the interval between the date of randomization until disease progression or death due to progression.

4. Overall Survival: Number of Participants Died Due to Any Cause [From randomization until death or as assessed up to 2 years post last participant last treatment visit]

5. Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow) [From randomization until death or as assessed up to 2 years post last participant last treatment visit]

6. Engraftment: Number of Participants Who Underwent Engraftment [From randomization until death or as assessed up to 2 years post last participant last treatment visit]

   Engraftment is the process of transplanted stem cells reproducing new cells.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously untreated, histologically confirmed multiple myeloma (per International Myeloma Working Group [IMWG] criteria

• Eastern Cooperative Oncology Group (ECOG) status 0-2

• Adequate absolute neutrophil count (ANC), platelet count and hemoglobin

• Adequate serum calcium

• Enrollment in System for Thalidomide Education and Prescribing Safety Program (S.T.E.P.S.)

Exclusion Criteria:

• No treatment with dexamethasone for multiple myeloma

• No peripheral neuropathy of Grade 2 or higher

• No Left Ventricular Ejection Fraction (LVEF) of less than 45 percentage

• No history of life-threatening thromboembolic events of any kind (ie, myocardial infarction, pulmonary embolism, stroke or others), within 1 year before enrollment in the study

• No deep vein thrombosis (DVT) within 1 year of enrollment

• No current anticoagulation for DVT

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Fountain Valley	California	United States
2		Greenbrae	California	United States
3		La Verne	California	United States
4		Los Angeles	California	United States
5		Denver	Colorado	United States
6		New London	Connecticut	United States
7		Boca Raton	Florida	United States
8		Jacksonville	Florida	United States
9		Miami	Florida	United States
10		Orange City	Florida	United States
11		Ormond Beach	Florida	United States
12		Lawrenceville	Georgia	United States
13		Chicago	Illinois	United States
14		Indianapolis	Indiana	United States
15		Wichita	Kansas	United States
16		Baltimore	Maryland	United States
17		Bethesda	Maryland	United States
18		Minneapolis	Minnesota	United States
19		St Louis Park	Minnesota	United States
20		Columbia	Missouri	United States
21		Kansas City	Missouri	United States
22		Omaha	Nebraska	United States
23		Englewood	New Jersey	United States
24		Hackensack	New Jersey	United States
25		Jersey City	New Jersey	United States
26		Voorhees	New Jersey	United States
27		Albany	New York	United States
28		Armonk	New York	United States
29		Box 302	New York	United States
30		Bronx	New York	United States
31		Brooklyn	New York	United States
32		Nyack	New York	United States
33		Valhalla	New York	United States
34		Durham	North Carolina	United States
35		Winston Salem	North Carolina	United States
36		Cleveland	Ohio	United States
37		Oklahoma City	Oklahoma	United States
38		Tulsa	Oklahoma	United States
39		Eugene	Oregon	United States
40		Pittsburgh	Pennsylvania	United States
41		Wynnewood	Pennsylvania	United States
42		Columbia	South Carolina	United States
43		Easley	South Carolina	United States
44		Sumter	South Carolina	United States
45		Memphis	Tennessee	United States
46		Nashville	Tennessee	United States
47		Bedford	Texas	United States
48		Dallas	Texas	United States
49		Fort Worth	Texas	United States
50		Fredericksburg	Texas	United States
51		Houston	Texas	United States
52		Burlington	Vermont	United States
53		Fairfax	Virginia	United States
54		Norfolk	Virginia	United States
55		Richmond	Virginia	United States
56		Spokane	Washington	United States
57		Vancouver	Washington	United States
58		Yakima	Washington	United States

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00097981
• Other Study ID Numbers: CR004579; DO04-23-006
• First Posted: Dec 2, 2004
• Last Update Posted: Apr 7, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Multiple myeloma; Newly diagnosed multiple myeloma; Thalidomide; Dexamethasone; DOXIL; Pegylated liposomal hydrochloride doxorubicin injection
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Dexamethasone

Study Results

Participant Flow

Pre-assignment Detail	A total of 225 participants were randomnly assigned to treatment, 113 participants to the thal/dex group and 112 participants to the DOXIL/thal/dex group.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Period Title: Overall Study
STARTED	113	112
Received Study Medication	110	106
COMPLETED	7	12
NOT COMPLETED	106	100

Baseline Characteristics

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone	Total
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	Total of all reporting groups
Overall Participants	113	112	225
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.29 (10.31)	60.62 (10.79)	60.45 (10.53)
Sex: Female, Male (Count of Participants)
Female	51 45.1%	44 39.3%	95 42.2%
Male	62 54.9%	68 60.7%	130 57.8%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate: Number of Participants Who Achieved a Complete Response
Description	Complete response rate to study medication is defined as number of participants who acheived complete response by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions. Complete response was assessed at the beginning of every treatment cycle prior to treatment, starting at Cycle 2.
Time Frame	From Cycle 2 until 28 days following completion of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	113	112
Number [Participants]	5 4.4%	8 7.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Thalidomide + Dexamethasone, DOXIL + Thalidomide + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by International Prognostic Index (IPI) stage 1,2 and 3

2. Secondary Outcome

Title	Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR)
Description	Overall response to study medication is defined as number of participants who acheived a complete response (CR) or partial response (PR) by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.
Time Frame	From Cycle 2 until 28 days following completion of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	113	112
Number [Participants]	81 71.7%	76 67.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Thalidomide + Dexamethasone, DOXIL + Thalidomide + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by International Prognostic Index (IPI) stage 1,2 and 3

3. Secondary Outcome

Title	Time to 1st Response
Description	Time to first response was defined as the interval from date of randomization to date of achieving a partial response (PR) or better according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.
Time Frame	From Cycle 2 until 28 days following completion of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	113	112
Median (95% Confidence Interval) [Days]	44	58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Thalidomide + Dexamethasone, DOXIL + Thalidomide + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Time to Progression
Description	Time to progression is the interval between the date of randomization until disease progression or death due to progression.
Time Frame	From randomization until death or as assessed up to 2 years post last participant last treatment visit

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	113	112
Median (95% Confidence Interval) [Days]	584	408

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Thalidomide + Dexamethasone, DOXIL + Thalidomide + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5162
	Comments
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Overall Survival: Number of Participants Died Due to Any Cause
Time Frame	From randomization until death or as assessed up to 2 years post last participant last treatment visit

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	113	112
Number [Participants]	21 18.6%	22 19.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Thalidomide + Dexamethasone, DOXIL + Thalidomide + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Log Rank
	Comments	Stratified log-rank test
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.975
	Confidence Interval	(2-Sided) 95%; 0.529 to 1.797
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow)
Time Frame	From randomization until death or as assessed up to 2 years post last participant last treatment visit

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	113	112
Number [Participants]	30 26.5%	28 25%

7. Secondary Outcome

Title	Engraftment: Number of Participants Who Underwent Engraftment
Description	Engraftment is the process of transplanted stem cells reproducing new cells.
Time Frame	From randomization until death or as assessed up to 2 years post last participant last treatment visit

Outcome Measure Data

Analysis Population Description

Intent-to-treat: Participants who were randomized to receive the treatment and who underwent transplantation.

Arm/Group Title	Thalidomide + Dexamethasone	DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.	DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
Measure Participants	30	28
Number [Participants]	25 22.1%	25 22.3%

Adverse Events

Time Frame	2 years
Arm/Group Title	Thalidomide + Dexamethasone		DOXIL + Thalidomide + Dexamethasone
Arm/Group Description	Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.		DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20.
All Cause Mortality
	Thalidomide + Dexamethasone		DOXIL + Thalidomide + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Thalidomide + Dexamethasone		DOXIL + Thalidomide + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/110 (43.6%)		53/106 (50%)
Blood and lymphatic system disorders
Anaemia	2/110 (1.8%)		3/106 (2.8%)
Coagulopathy	1/110 (0.9%)		2/106 (1.9%)
Disseminated Intravascular Coagulation	0/110 (0%)		1/106 (0.9%)
Febrile Neutropenia	1/110 (0.9%)		1/106 (0.9%)
Neutropenia	0/110 (0%)		2/106 (1.9%)
Pancytopenia	0/110 (0%)		1/106 (0.9%)
Thrombocytopenia	1/110 (0.9%)		2/106 (1.9%)
Cardiac disorders
Acute Myocardial Infarction	1/110 (0.9%)		0/106 (0%)
Angina Pectoris	1/110 (0.9%)		1/106 (0.9%)
Arrhythmia	0/110 (0%)		1/106 (0.9%)
Atrial Fibrillation	3/110 (2.7%)		3/106 (2.8%)
Bundle Branch Block Right	1/110 (0.9%)		0/106 (0%)
Cardiac Arrest	1/110 (0.9%)		0/106 (0%)
Cardiac Failure Congestive	1/110 (0.9%)		3/106 (2.8%)
Cardio-Respiratory Arrest	0/110 (0%)		1/106 (0.9%)
Coronary Artery Disease	0/110 (0%)		1/106 (0.9%)
Myocardial Infarction	2/110 (1.8%)		1/106 (0.9%)
Supraventricular Tachycardia	0/110 (0%)		3/106 (2.8%)
Gastrointestinal disorders
Abdominal Pain	1/110 (0.9%)		0/106 (0%)
Constipation	1/110 (0.9%)		0/106 (0%)
Duodenal Ulcer Haemorrhage	0/110 (0%)		1/106 (0.9%)
Gastrointestinal Haemorrhage	1/110 (0.9%)		2/106 (1.9%)
Gastrooesophageal Reflux Disease	1/110 (0.9%)		0/106 (0%)
Ileus	0/110 (0%)		1/106 (0.9%)
Intestinal Obstruction	0/110 (0%)		1/106 (0.9%)
Large Intestine Perforation	1/110 (0.9%)		0/106 (0%)
Nausea	1/110 (0.9%)		0/106 (0%)
Pancreatitis	1/110 (0.9%)		1/106 (0.9%)
Small Intestinal Obstruction	1/110 (0.9%)		0/106 (0%)
Stomatitis	1/110 (0.9%)		0/106 (0%)
Tongue Disorder	1/110 (0.9%)		0/106 (0%)
Vomiting	1/110 (0.9%)		0/106 (0%)
General disorders
Asthenia	3/110 (2.7%)		3/106 (2.8%)
Chest Pain	0/110 (0%)		1/106 (0.9%)
Chills	1/110 (0.9%)		0/106 (0%)
Disease Progression	0/110 (0%)		1/106 (0.9%)
Fatigue	1/110 (0.9%)		1/106 (0.9%)
Mass	1/110 (0.9%)		0/106 (0%)
Mucosal Inflammation	0/110 (0%)		1/106 (0.9%)
Non-Cardiac Chest Pain	1/110 (0.9%)		0/106 (0%)
Oedema	1/110 (0.9%)		0/106 (0%)
Oedema Peripheral	0/110 (0%)		1/106 (0.9%)
Pyrexia	1/110 (0.9%)		4/106 (3.8%)
Hepatobiliary disorders
Cholelithiasis	0/110 (0%)		1/106 (0.9%)
Infections and infestations
Abscess	1/110 (0.9%)		0/106 (0%)
Appendicitis	1/110 (0.9%)		0/106 (0%)
Bacteraemia	0/110 (0%)		2/106 (1.9%)
Bacterial Infection	0/110 (0%)		1/106 (0.9%)
Catheter Related Infection	0/110 (0%)		1/106 (0.9%)
Cellulitis	0/110 (0%)		1/106 (0.9%)
Diverticulitis	0/110 (0%)		1/106 (0.9%)
Endocarditis Enterococcal	1/110 (0.9%)		0/106 (0%)
Fungal Infection	0/110 (0%)		1/106 (0.9%)
Infection	0/110 (0%)		1/106 (0.9%)
Oesophageal Candidiasis	0/110 (0%)		1/106 (0.9%)
Pneumonia	5/110 (4.5%)		7/106 (6.6%)
Pneumonia Pneumococcal	1/110 (0.9%)		0/106 (0%)
Pneumonia Staphylococcal	1/110 (0.9%)		0/106 (0%)
Sepsis	3/110 (2.7%)		2/106 (1.9%)
Staphylococcal Infection	1/110 (0.9%)		0/106 (0%)
Urinary Tract Infection	1/110 (0.9%)		0/106 (0%)
Urosepsis	0/110 (0%)		1/106 (0.9%)
Injury, poisoning and procedural complications
Accidental Overdose	0/110 (0%)		1/106 (0.9%)
Compression Fracture	1/110 (0.9%)		0/106 (0%)
Fall	0/110 (0%)		1/106 (0.9%)
Hip Fracture	0/110 (0%)		1/106 (0.9%)
Spinal Compression Fracture	1/110 (0.9%)		0/106 (0%)
Investigations
Ejection Fraction Decreased	0/110 (0%)		1/106 (0.9%)
International Normalised Ratio Increased	1/110 (0.9%)		1/106 (0.9%)
Metabolism and nutrition disorders
Anorexia	0/110 (0%)		1/106 (0.9%)
Dehydration	4/110 (3.6%)		3/106 (2.8%)
Diabetes Mellitus	1/110 (0.9%)		0/106 (0%)
Diabetic Ketoacidosis	0/110 (0%)		1/106 (0.9%)
Electrolyte Imbalance	1/110 (0.9%)		0/106 (0%)
Hyperglycaemia	7/110 (6.4%)		1/106 (0.9%)
Hyperkalaemia	1/110 (0.9%)		1/106 (0.9%)
Hypocalcaemia	1/110 (0.9%)		1/106 (0.9%)
Hypoglycaemia	1/110 (0.9%)		1/106 (0.9%)
Hypokalaemia	1/110 (0.9%)		1/106 (0.9%)
Hyponatraemia	2/110 (1.8%)		1/106 (0.9%)
Hypovolaemia	0/110 (0%)		1/106 (0.9%)
Malnutrition	1/110 (0.9%)		0/106 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/110 (0%)		1/106 (0.9%)
Back Pain	0/110 (0%)		1/106 (0.9%)
Joint Effusion	0/110 (0%)		1/106 (0.9%)
Myopathy Steroid	1/110 (0.9%)		1/106 (0.9%)
Pain in Extremity	0/110 (0%)		1/106 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple Myeloma	0/110 (0%)		1/106 (0.9%)
Nervous system disorders
Cerebral Haemorrhage	0/110 (0%)		1/106 (0.9%)
Cerebrovascular Accident	0/110 (0%)		1/106 (0.9%)
Grand Mal Convulsion	0/110 (0%)		1/106 (0.9%)
Hemiparesis	0/110 (0%)		1/106 (0.9%)
Sleep Apnoea Syndrome	0/110 (0%)		1/106 (0.9%)
Syncope	4/110 (3.6%)		5/106 (4.7%)
Tremor	1/110 (0.9%)		0/106 (0%)
Psychiatric disorders
Anxiety	1/110 (0.9%)		0/106 (0%)
Psychotic Disorder	0/110 (0%)		1/106 (0.9%)
Renal and urinary disorders
Haematuria	0/110 (0%)		1/106 (0.9%)
Polyuria	1/110 (0.9%)		0/106 (0%)
Renal Failure	5/110 (4.5%)		3/106 (2.8%)
Renal Failure Acute	1/110 (0.9%)		2/106 (1.9%)
Reproductive system and breast disorders
Vaginal Haemorrhage	1/110 (0.9%)		0/106 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	0/110 (0%)		1/106 (0.9%)
Asthma	1/110 (0.9%)		0/106 (0%)
Bronchospasm	1/110 (0.9%)		0/106 (0%)
Chronic Obstructive Airways Disease Exacerbated	1/110 (0.9%)		0/106 (0%)
Chronic Obstructive Pulmonary Disease	0/110 (0%)		1/106 (0.9%)
Cryptogenic Organising Pneumonia	0/110 (0%)		1/106 (0.9%)
Dyspnoea	2/110 (1.8%)		1/106 (0.9%)
Hypoxia	0/110 (0%)		2/106 (1.9%)
Interstitial Lung Disease	0/110 (0%)		1/106 (0.9%)
Pleural Effusion	1/110 (0.9%)		0/106 (0%)
Pneumonitis	0/110 (0%)		1/106 (0.9%)
Pulmonary Embolism	6/110 (5.5%)		4/106 (3.8%)
Pulmonary Hypertension	0/110 (0%)		1/106 (0.9%)
Respiratory Distress	1/110 (0.9%)		0/106 (0%)
Respiratory Failure	0/110 (0%)		3/106 (2.8%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	0/110 (0%)		1/106 (0.9%)
Stevens-Johnson Syndrome	1/110 (0.9%)		0/106 (0%)
Surgical and medical procedures
Arthrectomy	1/110 (0.9%)		0/106 (0%)
Vascular disorders
Deep Vein Thrombosis	5/110 (4.5%)		4/106 (3.8%)
Haematoma	1/110 (0.9%)		0/106 (0%)
Haemorrhage	0/110 (0%)		1/106 (0.9%)
Hypertension	2/110 (1.8%)		1/106 (0.9%)
Hypotension	2/110 (1.8%)		1/106 (0.9%)
Orthostatic Hypotension	1/110 (0.9%)		0/106 (0%)
Shock	0/110 (0%)		1/106 (0.9%)
Thrombophlebitis	0/110 (0%)		1/106 (0.9%)
Other (Not Including Serious) Adverse Events
	Thalidomide + Dexamethasone		DOXIL + Thalidomide + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/110 (100%)		104/106 (98.1%)
Blood and lymphatic system disorders
Anaemia	21/110 (19.1%)		31/106 (29.2%)
Leukopenia	6/110 (5.5%)		2/106 (1.9%)
Neutropenia	4/110 (3.6%)		21/106 (19.8%)
Thrombocytopenia	6/110 (5.5%)		1/106 (0.9%)
Endocrine disorders
Cushingoid	5/110 (4.5%)		7/106 (6.6%)
Eye disorders
Vision Blurred	9/110 (8.2%)		16/106 (15.1%)
Gastrointestinal disorders
Abdominal Pain	4/110 (3.6%)		6/106 (5.7%)
Constipation	45/110 (40.9%)		48/106 (45.3%)
Diarrhoea	15/110 (13.6%)		16/106 (15.1%)
Dry Mouth	3/110 (2.7%)		7/106 (6.6%)
Dyspepsia	10/110 (9.1%)		6/106 (5.7%)
Dysphagia	3/110 (2.7%)		7/106 (6.6%)
Gastrooesophageal Reflux Disease	5/110 (4.5%)		8/106 (7.5%)
Nausea	26/110 (23.6%)		39/106 (36.8%)
Stomatitis	4/110 (3.6%)		14/106 (13.2%)
Vomiting	13/110 (11.8%)		15/106 (14.2%)
General disorders
Asthenia	19/110 (17.3%)		13/106 (12.3%)
Fatigue	58/110 (52.7%)		58/106 (54.7%)
Mucosal Inflammation	4/110 (3.6%)		20/106 (18.9%)
Oedema	12/110 (10.9%)		16/106 (15.1%)
Oedema Peripheral	53/110 (48.2%)		60/106 (56.6%)
Pyrexia	14/110 (12.7%)		16/106 (15.1%)
Infections and infestations
Candidiasis	3/110 (2.7%)		9/106 (8.5%)
Oral Candidiasis	2/110 (1.8%)		7/106 (6.6%)
Upper Respiratory Tract Infection	9/110 (8.2%)		14/106 (13.2%)
Investigations
International Normalised Ratio Increased	7/110 (6.4%)		8/106 (7.5%)
Weight Decreased	9/110 (8.2%)		9/106 (8.5%)
Weight Increased	7/110 (6.4%)		5/106 (4.7%)
Metabolism and nutrition disorders
Anorexia	12/110 (10.9%)		16/106 (15.1%)
Decreased Appetite	9/110 (8.2%)		10/106 (9.4%)
Dehydration	10/110 (9.1%)		10/106 (9.4%)
Diabetes Mellitus	7/110 (6.4%)		4/106 (3.8%)
Hyperglycaemia	19/110 (17.3%)		18/106 (17%)
Hypocalcaemia	10/110 (9.1%)		10/106 (9.4%)
Hypokalaemia	13/110 (11.8%)		11/106 (10.4%)
Hyponatraemia	6/110 (5.5%)		4/106 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/110 (14.5%)		15/106 (14.2%)
Back Pain	16/110 (14.5%)		16/106 (15.1%)
Bone Pain	5/110 (4.5%)		9/106 (8.5%)
Joint Swelling	3/110 (2.7%)		6/106 (5.7%)
Muscle Spasms	9/110 (8.2%)		4/106 (3.8%)
Muscular Weakness	12/110 (10.9%)		10/106 (9.4%)
Musculoskeletal Chest Pain	9/110 (8.2%)		4/106 (3.8%)
Myalgia	9/110 (8.2%)		6/106 (5.7%)
Pain in Extremity	14/110 (12.7%)		13/106 (12.3%)
Nervous system disorders
Dizziness	27/110 (24.5%)		23/106 (21.7%)
Dysgeusia	10/110 (9.1%)		16/106 (15.1%)
Headache	18/110 (16.4%)		4/106 (3.8%)
Hypoaesthesia	16/110 (14.5%)		14/106 (13.2%)
Neuropathy	13/110 (11.8%)		15/106 (14.2%)
Neuropathy Peripheral	22/110 (20%)		17/106 (16%)
Paraesthesia	16/110 (14.5%)		13/106 (12.3%)
Peripheral Sensory Neuropathy	14/110 (12.7%)		12/106 (11.3%)
Somnolence	13/110 (11.8%)		2/106 (1.9%)
Tremor	20/110 (18.2%)		22/106 (20.8%)
Psychiatric disorders
Anxiety	16/110 (14.5%)		16/106 (15.1%)
Confusional State	8/110 (7.3%)		4/106 (3.8%)
Depression	15/110 (13.6%)		15/106 (14.2%)
Insomnia	24/110 (21.8%)		16/106 (15.1%)
Respiratory, thoracic and mediastinal disorders
Cough	11/110 (10%)		10/106 (9.4%)
Dyspnoea	22/110 (20%)		24/106 (22.6%)
Dyspnoea Exertional	5/110 (4.5%)		6/106 (5.7%)
Epistaxis	3/110 (2.7%)		6/106 (5.7%)
Pharyngolaryngeal Pain	5/110 (4.5%)		8/106 (7.5%)
Skin and subcutaneous tissue disorders
Alopecia	3/110 (2.7%)		7/106 (6.6%)
Dry Skin	3/110 (2.7%)		11/106 (10.4%)
Erythema	7/110 (6.4%)		7/106 (6.6%)
Palmar-Plantar Erythrodysaesthesia Syndrome	3/110 (2.7%)		39/106 (36.8%)
Rash	20/110 (18.2%)		20/106 (18.9%)
Vascular disorders
Deep Vein Thrombosis	4/110 (3.6%)		10/106 (9.4%)
Hypertension	2/110 (1.8%)		9/106 (8.5%)
Hypotension	5/110 (4.5%)		6/106 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.