Trial Outcomes & Findings for Zoledronate With or Without Thalidomide in Treating Patients With Early Stage Multiple Myeloma (NCT NCT00432458)
NCT ID: NCT00432458
Last Updated: 2012-07-04
Results Overview
Time to disease progression (TTP) was defined as the time from randomization to the earliest documentation of disease progression. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method, a two-sided (stratified) log-rank test was calculated.
COMPLETED
PHASE3
68 participants
randomization to progression (up to 5 years)
2012-07-04
Participant Flow
Sixty-eight (68) participants were recruited at Mayo Clinic (Rochester) and Memorial Sloan-Kettering between July 2003 and March 2009.
All 68 participants were randomized.
Participant milestones
| Measure |
Arm I: Thal/ZLD
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
Zoledronic acid (ZLD)
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
33
|
|
Overall Study
COMPLETED
|
30
|
32
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Zoledronate With or Without Thalidomide in Treating Patients With Early Stage Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Arm I: Thal/ZLD
n=35 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 Participants
Zoledronic acid (ZLD)
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
63 years
n=5 Participants
|
63 years
n=7 Participants
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=5 Participants
|
33 participants
n=7 Participants
|
68 participants
n=5 Participants
|
|
Beta-2 Microglobulin
High (> upper limit of normal)
|
29 participants
n=5 Participants
|
26 participants
n=7 Participants
|
55 participants
n=5 Participants
|
|
Beta-2 Microglobulin
Normal (<= upper limit of normal)
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Lytic Bone Lesions
Present
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Lytic Bone Lesions
Not Present
|
33 participants
n=5 Participants
|
31 participants
n=7 Participants
|
64 participants
n=5 Participants
|
|
Bone Marrow Labeling Index
High (> 1.0%)
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Bone Marrow Labeling Index
Low (<= 1.0%)
|
31 participants
n=5 Participants
|
30 participants
n=7 Participants
|
61 participants
n=5 Participants
|
|
Bone Marrow Labeling Index
Not Applicable
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Anemia
< lower limit of normal
|
14 participants
n=5 Participants
|
18 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Anemia
>= lower limit of normal
|
21 participants
n=5 Participants
|
15 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Peripheral blood circulating plasma cells
Yes
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Peripheral blood circulating plasma cells
No
|
20 participants
n=5 Participants
|
18 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Peripheral blood circulating plasma cells
Not Applicable
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Peripheral blood circulating plasma cells
Not Done
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: randomization to progression (up to 5 years)Population: Time to disease progression was analyzed on all randomized participants on an intent to treat basis.
Time to disease progression (TTP) was defined as the time from randomization to the earliest documentation of disease progression. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method, a two-sided (stratified) log-rank test was calculated.
Outcome measures
| Measure |
Arm I: Thal/ZLD
n=35 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 Participants
Zoledronic acid (ZLD)
|
|---|---|---|
|
Time to Disease Progression (TTP)
|
2.4 years
Interval 1.4 to 3.6
|
1.2 years
Interval 0.7 to 2.5
|
SECONDARY outcome
Timeframe: 12 monthsPFS at 12 months is a dichotomized outcome indicating whether or not a participant was progression free (and alive) at 12 months from the date of randomization.
Outcome measures
| Measure |
Arm I: Thal/ZLD
n=35 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 Participants
Zoledronic acid (ZLD)
|
|---|---|---|
|
12-month Progression-free Survival (PFS)
|
30 participants
|
18 participants
|
SECONDARY outcome
Timeframe: 12 monthsResponse is defined as follows: * CR: Complete disappearance of M-protein from serum \& urine on immunofixation, \<5% plasma cells in bone marrow (BM) * VGPR: \>=90% reduction in serum M-component; Urine M-Component \<100 mg per 24 hours; \<=5% plasma cells in BM * PR: \>= 50% reduction in serum M-Component and/or Urine M-Component \>= 90% reduction or \<200 mg per 24 hours; or \>= 50% decrease in difference between involved and uninvolved FLC levels
Outcome measures
| Measure |
Arm I: Thal/ZLD
n=35 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 Participants
Zoledronic acid (ZLD)
|
|---|---|---|
|
Number of Participants With a Confirmed Response (Complete Response [CR], Very Good Partial Response [VGPR] or Partial Response [PR]) on Two Consecutive Evaluations at Least 2 Weeks Apart in the First 12 Months of Treatment
|
13 participants
|
0 participants
|
SECONDARY outcome
Timeframe: time from start of response to progression (up to 5 years)Population: Participants who achieved a confirmed response (CR, VGPR, or PR) as described above were analyzed.
Duration of response (DOR) is defined as the time from first documentation of response (CR, VGPR or PR) to disease progression. The median DOR with 95% CI was estimated using the Kaplan Meier method
Outcome measures
| Measure |
Arm I: Thal/ZLD
n=13 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
Zoledronic acid (ZLD)
|
|---|---|---|
|
Duration of Response (Complete Response, Partial Response, and Very Good Partial Response)
|
3.3 years
Interval 1.1 to
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment
|
—
|
SECONDARY outcome
Timeframe: time from end of treatment to subsequent treatment (up to 5 years)Population: This data was not (and will never be) analyzed as it was not submitted consistently across all participants.
Time to subsequent treatment (TTS) was defined as time from end of active (protocol) treatment to the start of subsequent treatment for participants with progressive disease. The median TTS with 95% CI was estimated using the Kaplan Meier method
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: time from randomization to treatment failure (up to 5 years)Time to treatment failure (TTF) was defined as the time from randomization to the date at which the patient was removed from (protocol) treatment due to disease progression, unacceptable toxicity, participant refusal or death. The median TTF with 95% CI was estimated using the Kaplan Meier method
Outcome measures
| Measure |
Arm I: Thal/ZLD
n=35 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 Participants
Zoledronic acid (ZLD)
|
|---|---|---|
|
Time to Treatment Failure
|
16.5 months
Interval 9.5 to 27.6
|
11.1 months
Interval 8.4 to 16.7
|
SECONDARY outcome
Timeframe: During treatment (up to 5 years)Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 2. Description of Grades: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death
Outcome measures
| Measure |
Arm I: Thal/ZLD
n=35 Participants
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 Participants
Zoledronic acid (ZLD)
|
|---|---|---|
|
Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events
|
17 participants
|
13 participants
|
Adverse Events
Arm I: Thal/ZLD
Arm II: ZLD
Serious adverse events
| Measure |
Arm I: Thal/ZLD
n=35 participants at risk
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 participants at risk
Zoledronic acid (ZLD)
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Infection without neutropenia
|
2.9%
1/35 • Number of events 2
|
0.00%
0/33
|
|
Renal and urinary disorders
Ureteral Obstruction
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
0.00%
0/35
|
3.0%
1/33 • Number of events 2
|
Other adverse events
| Measure |
Arm I: Thal/ZLD
n=35 participants at risk
Thalidomide (Thal) + Zolendronic acid (ZLD)
|
Arm II: ZLD
n=33 participants at risk
Zoledronic acid (ZLD)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.7%
2/35 • Number of events 2
|
3.0%
1/33 • Number of events 5
|
|
Cardiac disorders
Cardiovascular
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Cardiac disorders
Ischemia/Infarction
|
5.7%
2/35 • Number of events 2
|
0.00%
0/33
|
|
Cardiac disorders
Sinus bradycardia
|
5.7%
2/35 • Number of events 3
|
0.00%
0/33
|
|
Cardiac disorders
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)
|
5.7%
2/35 • Number of events 2
|
0.00%
0/33
|
|
Cardiac disorders
Ventricular arrhythmia
|
5.7%
2/35 • Number of events 2
|
0.00%
0/33
|
|
Ear and labyrinth disorders
Otitis External
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Eye disorders
Vision
|
0.00%
0/35
|
3.0%
1/33 • Number of events 2
|
|
Gastrointestinal disorders
Colitis
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Gastrointestinal disorders
Constipation
|
62.9%
22/35 • Number of events 189
|
18.2%
6/33 • Number of events 29
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
General disorders
Fatigue
|
77.1%
27/35 • Number of events 133
|
60.6%
20/33 • Number of events 64
|
|
General disorders
Fever-No ANC
|
2.9%
1/35 • Number of events 1
|
9.1%
3/33 • Number of events 3
|
|
General disorders
Pain
|
5.7%
2/35 • Number of events 2
|
3.0%
1/33 • Number of events 1
|
|
General disorders
Rigors
|
5.7%
2/35 • Number of events 2
|
0.00%
0/33
|
|
Infections and infestations
Infection
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Infections and infestations
Infection without neutropenia
|
22.9%
8/35 • Number of events 12
|
6.1%
2/33 • Number of events 4
|
|
Investigations
Aspartate aminotransferase increased
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Investigations
CD4 lymphocytes decreased
|
2.9%
1/35 • Number of events 3
|
0.00%
0/33
|
|
Investigations
CPK (creatine phosphokinase)
|
0.00%
0/35
|
3.0%
1/33 • Number of events 3
|
|
Investigations
Creatinine
|
0.00%
0/35
|
6.1%
2/33 • Number of events 2
|
|
Investigations
Leukopenia
|
8.6%
3/35 • Number of events 13
|
0.00%
0/33
|
|
Investigations
Lymphopenia
|
5.7%
2/35 • Number of events 12
|
3.0%
1/33 • Number of events 1
|
|
Investigations
Neutropenia
|
37.1%
13/35 • Number of events 59
|
6.1%
2/33 • Number of events 6
|
|
Investigations
Prothrombin Time
|
2.9%
1/35 • Number of events 1
|
3.0%
1/33 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.7%
2/35 • Number of events 4
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/35
|
6.1%
2/33 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
2.9%
1/35 • Number of events 2
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.9%
1/35 • Number of events 1
|
6.1%
2/33 • Number of events 2
|
|
Nervous system disorders
Ataxia
|
5.7%
2/35 • Number of events 2
|
0.00%
0/33
|
|
Nervous system disorders
Depressed level of consciousness
|
51.4%
18/35 • Number of events 48
|
3.0%
1/33 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
5.7%
2/35 • Number of events 2
|
3.0%
1/33 • Number of events 1
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Nervous system disorders
Ischemia-Cerebral
|
2.9%
1/35 • Number of events 1
|
3.0%
1/33 • Number of events 1
|
|
Nervous system disorders
Neuro-Cranial
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Nervous system disorders
Peripheral motor neuropathy
|
11.4%
4/35 • Number of events 5
|
0.00%
0/33
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
80.0%
28/35 • Number of events 304
|
18.2%
6/33 • Number of events 10
|
|
Nervous system disorders
Seizure
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Nervous system disorders
Syncope
|
8.6%
3/35 • Number of events 5
|
0.00%
0/33
|
|
Nervous system disorders
Tremor
|
2.9%
1/35 • Number of events 3
|
3.0%
1/33 • Number of events 1
|
|
Nervous system disorders
Vasovagal Episode
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Psychiatric disorders
Depression
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Renal and urinary disorders
Ureteral Obstruction
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.9%
1/35 • Number of events 1
|
0.00%
0/33
|
|
Skin and subcutaneous tissue disorders
Rash/Desquamation
|
28.6%
10/35 • Number of events 24
|
24.2%
8/33 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
Rash/dermatitis associated with high-dose chemotherapy or BMT studies.
|
0.00%
0/35
|
3.0%
1/33 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
2.9%
1/35 • Number of events 1
|
3.0%
1/33 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place