Thalidomide and Prednisone After Autologous Stem Cell Transplantation Multiple Myeloma

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00049673
• Collaborator: National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other)
• Enrollment: 332
• Locations: 18
• Arms: 2
• Actual Duration (Months): 132.1
• Patients Per Site: 18.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Thalidomide may stop the growth of multiple myeloma by stopping blood flow to the tumor. It is not yet known whether combining thalidomide with prednisone and giving them after autologous stem cell transplantation may be effective in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying thalidomide and prednisone to see how well they work compared to observation in treating patients who have undergone stem cell transplantation for multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: prednisone; Drug: thalidomide	Phase 3

Detailed Description

OBJECTIVES:

• Compare overall survival of patients with multiple myeloma treated with thalidomide and prednisone as maintenance therapy vs observation alone after autologous stem cell transplantation.

• Compare progression-free survival of patients treated with these regimens.

• Compare quality of life of patients treated with these regimens.

• Compare toxic effects of these regimens in these patients.

• Compare the objective venous thromboembolism rate in symptomatic patients treated with these regimens.

OUTLINE: This is a randomized, non-blinded, multicenter study. Patients are stratified according to treatment center, age (under 60 vs 60 and over), and response to prior transplantation (complete vs incomplete). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo observation.

For both arms, patients are assessed (including for quality of life) regularly throughout the treatment/observation period: at baseline, every 2 months for 6 months, every 3 months for up to 4 years, and then annually thereafter.

After the treatment/observation period, patients are followed annually..

PROJECTED ACCRUAL: A total of 324 patients will be accrued for this study within 3.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 332 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Study Of Thalidomide And Prednisone As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients With Multiple Myeloma
• Actual Study Start Date: Sep 16, 2002
• Actual Primary Completion Date: Jul 7, 2010
• Actual Study Completion Date: Sep 19, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity.	Drug: prednisone; Given orally; Drug: thalidomide; Given orally
No Intervention: Arm II Patients undergo observation.

Outcome Measures

Primary Outcome Measures

1. Overall Survival [11 years]

   Number of patients died from any cause during the study.

Secondary Outcome Measures

1. Disease Progression-free Survival [11 years]

   Number of patients with disease progression or death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed multiple myeloma as evidenced by one of the following:

• Biopsy of an osteolytic lesion or soft tissue tumor composed of plasma cells

• Bone marrow aspirate and/or biopsy demonstrating at least 10% plasmacytosis

• Bone marrow less than 10% plasma cells with at least 1 bony lesion and meets the M-protein criteria as below

• Detectable serum M-component of IgG, IgA, IgD, or IgE at initial diagnosis OR

• Urinary excretion of light chain (Bence Jones) protein at least 1.0 gm/24 hrs if only light chain disease (urine M-protein) was present at initial diagnosis

• Previously treated with autologous stem cell transplantation after high-dose melphalan (200 mg/m^2) within the past 60-100 days

• Received transplantation within 1 year of the beginning of initial chemotherapy for multiple myeloma

• No evidence of disease progression

PATIENT CHARACTERISTICS:

Age

• 16 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• No prior hereditary hypercoaguable disorder

• Granulocyte count at least 1,000/mm^3

• Platelet count at least 75,000/mm^3

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)

• AST and/or ALT no greater than 2 times ULN

• Alkaline phosphatase no greater than 2 times ULN

Renal

• Creatinine no greater than 3 times ULN

Cardiovascular

• No prior spontaneous deep vein thrombosis within the past 5 years

• Catheter-associated thrombus allowed

• No uncontrolled hypertension

Pulmonary

• No prior pulmonary embolism within the past 5 years

Other

• No other prior or concurrent malignancy except adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or any cancer treated more than 5 years prior to study entry and presumed cured

• No prior gastric ulceration or bleeding within the past 5 years

• No prior documented lupus anti-coagulant or anti-phospholipid antibody

• Not pregnant or nursing

• Negative pregnancy test

• Fertile female patients must use 2 effective methods of contraception for 1 month prior, during, and 1 month after study participation

• Male patients must use effective barrier contraception during and for 1 month after study participation

• No avascular necrosis of the hips or shoulders

• No grade 2 or greater peripheral neuropathy causing symptomatic dysfunction (vincristine-induced sensory symptoms allowed)

• No diabetes with end-organ damage defined as:

• Documented diabetic neuropathy

• Retinal vascular proliferation requiring treatment

• Cardiovascular disease requiring active therapy

• Willing to complete quality of life questionnaires

• Employment does not prohibit the use of sedatives

• No other major medical illness or condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• No prior double autologous or allogeneic hematopoietic stem cell transplantation

• No prior thalidomide

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other concurrent anti-cancer therapy

• No other concurrent investigational therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
2	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
3	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
4	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
5	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
6	Atlantic Health Sciences Corporation	Saint John	New Brunswick	Canada	E2L 4L2
7	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	AIB 3V6
8	QEII Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
9	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
10	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario	Canada	K7L 5P9
11	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
12	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
13	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
14	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
15	McGill University - Dept. Oncology	Montreal	Quebec	Canada	H2W 1S6
16	CHA-Hopital Du St-Sacrement	Quebec City	Quebec	Canada	G1S 4L8
17	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
18	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

• NCIC Clinical Trials Group
• National Cancer Institute (NCI)
• Eastern Cooperative Oncology Group

Investigators

• Study Chair: A. Keith Stewart, MD, Mayo Clinic
• Study Chair: Martha Q. Lacy, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00049673
• Other Study ID Numbers: MY10; CAN-NCIC-JMY10; ECOG-NCIC-JMY10; CELGENE-CAN-NCIC-MY10; CDR0000258158
• First Posted: Jan 27, 2003
• Last Update Posted: Oct 5, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by NCIC Clinical Trials Group: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Thalidomide; Prednisone

Study Results

Participant Flow

Arm/Group Title	Prednisone	Observation
Arm/Group Description	Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity. prednisone: Given orally thalidomide: Given orally	Patients undergo observation.
Period Title: Overall Study
STARTED	166	166
COMPLETED	165	163
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Prednisone	Observation	Total
Arm/Group Description	Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity. prednisone: Given orally thalidomide: Given orally	Patients undergo observation.	Total of all reporting groups
Overall Participants	166	166	332
Age, Customized (Count of Participants)
Age < 60	102 61.4%	103 62%	205 61.7%
Age > or = 60	64 38.6%	63 38%	127 38.3%
Sex: Female, Male (Count of Participants)
Female	58 34.9%	56 33.7%	114 34.3%
Male	108 65.1%	110 66.3%	218 65.7%
Region of Enrollment (participants) [Number]
Canada	162 97.6%	162 97.6%	324 97.6%
United States	4 2.4%	4 2.4%	8 2.4%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Number of patients died from any cause during the study.
Time Frame	11 years

Outcome Measure Data

Analysis Population Description

Intention-to-treat population

Arm/Group Title	Prednisone	Observation
Arm/Group Description	Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity. prednisone: Given orally thalidomide: Given orally	Patients undergo observation.
Measure Participants	166	166
Death	50 30.1%	61 36.7%
Alive	116 69.9%	105 63.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prednisone, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Disease Progression-free Survival
Description	Number of patients with disease progression or death
Time Frame	11 years

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Prednisone	Observation
Arm/Group Description	Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity. prednisone: Given orally thalidomide: Given orally	Patients undergo observation.
Measure Participants	166	166
Disease progression	100 60.2%	127 76.5%
Without progression	66 39.8%	39 23.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prednisone, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	11 years
Arm/Group Title	Prednisone		Observation
Arm/Group Description	Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity. prednisone: Given orally thalidomide: Given orally		Patients undergo observation.
All Cause Mortality
	Prednisone		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/166 (30.1%)		61/166 (36.7%)
Serious Adverse Events
	Prednisone		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/165 (3%)		2/163 (1.2%)
Cardiac disorders
Sinus bradycardia	1/165 (0.6%)		0/163 (0%)
Gastrointestinal disorders
Colitis	1/165 (0.6%)		0/163 (0%)
Immune system disorders
Other	1/165 (0.6%)		1/163 (0.6%)
Nervous system disorders
Syncope	1/165 (0.6%)		0/163 (0%)
Renal and urinary disorders
Renal failure	0/165 (0%)		1/163 (0.6%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/165 (0.6%)		0/163 (0%)
Other (Not Including Serious) Adverse Events
	Prednisone		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	165/165 (100%)		158/163 (96.9%)
Cardiac disorders
Edema	72/165 (43.6%)		29/163 (17.8%)
Ear and labyrinth disorders
Inner ear/hearing	25/165 (15.2%)		4/163 (2.5%)
Endocrine disorders
Cushingoid appearance	25/165 (15.2%)		0/163 (0%)
Eye disorders
Blurred vision	31/165 (18.8%)		5/163 (3.1%)
Cataract	18/165 (10.9%)		1/163 (0.6%)
Gastrointestinal disorders
Constipation	97/165 (58.8%)		32/163 (19.6%)
Diarrhea	31/165 (18.8%)		36/163 (22.1%)
Mouth dryness	55/165 (33.3%)		5/163 (3.1%)
Dyspepsia/heartburn	41/165 (24.8%)		17/163 (10.4%)
Nausea	37/165 (22.4%)		28/163 (17.2%)
Stomatitis	14/165 (8.5%)		9/163 (5.5%)
Vomiting	16/165 (9.7%)		19/163 (11.7%)
Other	23/165 (13.9%)		6/163 (3.7%)
Abdominal pain	30/165 (18.2%)		24/163 (14.7%)
General disorders
Fatigue	120/165 (72.7%)		95/163 (58.3%)
Other	28/165 (17%)		23/163 (14.1%)
Chest pain	18/165 (10.9%)		7/163 (4.3%)
Pain-Other	45/165 (27.3%)		22/163 (13.5%)
Immune system disorders
Allergic reaction	12/165 (7.3%)		6/163 (3.7%)
Fever	22/165 (13.3%)		16/163 (9.8%)
Other	20/165 (12.1%)		11/163 (6.7%)
Infections and infestations
Infection w/o neutropen	113/165 (68.5%)		88/163 (54%)
Infection-unknown ANC	11/165 (6.7%)		7/163 (4.3%)
Injury, poisoning and procedural complications
Bruising	14/165 (8.5%)		1/163 (0.6%)
Investigations
Hypercholesterolemia	15/165 (9.1%)		3/163 (1.8%)
Metabolism and nutrition disorders
Anorexia	16/165 (9.7%)		15/163 (9.2%)
Musculoskeletal and connective tissue disorders
Muscle weakness	32/165 (19.4%)		9/163 (5.5%)
Other	34/165 (20.6%)		22/163 (13.5%)
Arthralgia	36/165 (21.8%)		40/163 (24.5%)
Myalgia	74/165 (44.8%)		51/163 (31.3%)
Bone pain	119/165 (72.1%)		121/163 (74.2%)
Nervous system disorders
Taste disturbance	15/165 (9.1%)		7/163 (4.3%)
Dizziness	70/165 (42.4%)		15/163 (9.2%)
Memory loss	19/165 (11.5%)		3/163 (1.8%)
Neuropathy-motor	13/165 (7.9%)		4/163 (2.5%)
Neuropathy-sensory	147/165 (89.1%)		71/163 (43.6%)
Depressed conscious.	29/165 (17.6%)		5/163 (3.1%)
Tremor	33/165 (20%)		2/163 (1.2%)
Headache	24/165 (14.5%)		19/163 (11.7%)
Neuropathic pain	16/165 (9.7%)		12/163 (7.4%)
Psychiatric disorders
Anxiety	63/165 (38.2%)		22/163 (13.5%)
Confusion	17/165 (10.3%)		2/163 (1.2%)
Insomnia	69/165 (41.8%)		44/163 (27%)
Depression	28/165 (17%)		27/163 (16.6%)
Renal and urinary disorders
Urine frequency/urgency	14/165 (8.5%)		12/163 (7.4%)
Reproductive system and breast disorders
Erectile impotence	11/165 (6.7%)		4/163 (2.5%)
Respiratory, thoracic and mediastinal disorders
Cough	52/165 (31.5%)		38/163 (23.3%)
Dyspnea	69/165 (41.8%)		33/163 (20.2%)
Other	13/165 (7.9%)		7/163 (4.3%)
Skin and subcutaneous tissue disorders
Sweating	27/165 (16.4%)		12/163 (7.4%)
Dry skin	28/165 (17%)		17/163 (10.4%)
Nail changes	9/165 (5.5%)		5/163 (3.1%)
Pruritus	18/165 (10.9%)		16/163 (9.8%)
Rash/desquamation	60/165 (36.4%)		39/163 (23.9%)
Other	14/165 (8.5%)		11/163 (6.7%)
Vascular disorders
Hypertension	27/165 (16.4%)		13/163 (8%)
Thrombosis/embolism	12/165 (7.3%)		1/163 (0.6%)
Hot flashes/ flushes	15/165 (9.1%)		6/163 (3.7%)
Flushing	9/165 (5.5%)		1/163 (0.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.