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Trial record 7 of 2570 for:    "Plasma Cell Neoplasm"

Zoledronate With or Without Thalidomide in Treating Patients With Early Stage Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00432458
Recruitment Status : Completed
First Posted : February 7, 2007
Results First Posted : July 4, 2012
Last Update Posted : July 4, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma and Plasma Cell Neoplasm
Interventions Drug: Thalidomide
Drug: zoledronic acid
Enrollment 68
Recruitment Details Sixty-eight (68) participants were recruited at Mayo Clinic (Rochester) and Memorial Sloan-Kettering between July 2003 and March 2009.
Pre-assignment Details All 68 participants were randomized.
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description Thalidomide (Thal) + Zolendronic acid (ZLD) Zoledronic acid (ZLD)
Period Title: Overall Study
Started 35 33
Completed 30 32
Not Completed 5 1
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD Total
Hide Arm/Group Description Thalidomide (Thal) + Zolendronic acid (ZLD) Zoledronic acid (ZLD) Total of all reporting groups
Overall Number of Baseline Participants 35 33 68
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants 33 participants 68 participants
63
(47 to 84)
63
(47 to 80)
63
(47 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 33 participants 68 participants
Female
13
  37.1%
14
  42.4%
27
  39.7%
Male
22
  62.9%
19
  57.6%
41
  60.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 35 participants 33 participants 68 participants
35 33 68
Beta-2 Microglobulin   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 33 participants 68 participants
High (> upper limit of normal) 29 26 55
Normal (<= upper limit of normal) 6 7 13
[1]
Measure Description: The upper limit of normal for Beta-2 microglobulin was 1.80 mcg/mL.
Lytic Bone Lesions  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 33 participants 68 participants
Present 2 2 4
Not Present 33 31 64
Bone Marrow Labeling Index   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 33 participants 68 participants
High (> 1.0%) 3 3 6
Low (<= 1.0%) 31 30 61
Not Applicable 1 0 1
[1]
Measure Description: The labeling index indicates how fast the cancer cells are growing. This test is done in specialized labs, using myeloma cells from bone marrow samples. A high labeling index can predict a more rapid accumulation of cancer cells and a worse outlook.
Anemia   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 33 participants 68 participants
< lower limit of normal 14 18 32
>= lower limit of normal 21 15 36
[1]
Measure Description: The lower limit of normal (LLN) is institution specific, typically about 13.5 g/dL for males and 12.0 g/dL for females.
Peripheral blood circulating plasma cells   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 33 participants 68 participants
Yes 13 14 27
No 20 18 38
Not Applicable 1 0 1
Not Done 1 1 2
[1]
Measure Description: Peripheral blood circulating plasma cells are cells which live outside of the bone marrow.
1.Primary Outcome
Title Time to Disease Progression (TTP)
Hide Description 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.
Time Frame randomization to progression (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Time to disease progression was analyzed on all randomized participants on an intent to treat basis.
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 35 33
Median (95% Confidence Interval)
Unit of Measure: years
2.4
(1.4 to 3.6)
1.2
(0.7 to 2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I: Thal/ZLD, Arm II: ZLD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Log Rank
Comments Model was stratified by beta-2 microglobulin (high vs low), lytic bone lesions (present vs not) and bone marrow labeling index (high vs low)
2.Secondary Outcome
Title 12-month Progression-free Survival (PFS)
Hide Description PFS 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 35 33
Measure Type: Number
Unit of Measure: participants
30 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I: Thal/ZLD, Arm II: ZLD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0048
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
3.Secondary Outcome
Title 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
Hide Description

Response 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
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 35 33
Measure Type: Number
Unit of Measure: participants
13 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I: Thal/ZLD, Arm II: ZLD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response (Complete Response, Partial Response, and Very Good Partial Response)
Hide Description 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
Time Frame time from start of response to progression (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who achieved a confirmed response (CR, VGPR, or PR) as described above were analyzed.
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 13 0
Median (95% Confidence Interval)
Unit of Measure: years
3.3 [1] 
(1.1 to NA)
[1]
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment
5.Secondary Outcome
Title Time to Subsequent Treatment
Hide Description 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
Time Frame time from end of treatment to subsequent treatment (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not (and will never be) analyzed as it was not submitted consistently across all participants.
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Time to Treatment Failure
Hide Description 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
Time Frame time from randomization to treatment failure (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 35 33
Median (95% Confidence Interval)
Unit of Measure: months
16.5
(9.5 to 27.6)
11.1
(8.4 to 16.7)
7.Secondary Outcome
Title Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events
Hide Description

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

Time Frame During treatment (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description:
Thalidomide (Thal) + Zolendronic acid (ZLD)
Zoledronic acid (ZLD)
Overall Number of Participants Analyzed 35 33
Measure Type: Number
Unit of Measure: participants
17 13
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I: Thal/ZLD Arm II: ZLD
Hide Arm/Group Description Thalidomide (Thal) + Zolendronic acid (ZLD) Zoledronic acid (ZLD)
All-Cause Mortality
Arm I: Thal/ZLD Arm II: ZLD
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I: Thal/ZLD Arm II: ZLD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/35 (8.57%)      1/33 (3.03%)    
Ear and labyrinth disorders     
Vertigo  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Infections and infestations     
Infection without neutropenia  1  1/35 (2.86%)  2 0/33 (0.00%)  0
Renal and urinary disorders     
Ureteral Obstruction  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Dyspnea  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Pulmonary  1  0/35 (0.00%)  0 1/33 (3.03%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 5
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I: Thal/ZLD Arm II: ZLD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/35 (100.00%)      28/33 (84.85%)    
Blood and lymphatic system disorders     
Anemia  1  2/35 (5.71%)  2 1/33 (3.03%)  5
Cardiac disorders     
Cardiovascular  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Ischemia/Infarction  1  2/35 (5.71%)  2 0/33 (0.00%)  0
Sinus bradycardia  1  2/35 (5.71%)  3 0/33 (0.00%)  0
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)  1  2/35 (5.71%)  2 0/33 (0.00%)  0
Ventricular arrhythmia  1  2/35 (5.71%)  2 0/33 (0.00%)  0
Ear and labyrinth disorders     
Otitis External  1  0/35 (0.00%)  0 1/33 (3.03%)  1
Eye disorders     
Conjunctivitis  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Vision  1  0/35 (0.00%)  0 1/33 (3.03%)  2
Gastrointestinal disorders     
Colitis  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Constipation  1  22/35 (62.86%)  189 6/33 (18.18%)  29
Gastrointestinal disorder  1  1/35 (2.86%)  1 0/33 (0.00%)  0
General disorders     
Fatigue  1  27/35 (77.14%)  133 20/33 (60.61%)  64
Fever-No ANC  1  1/35 (2.86%)  1 3/33 (9.09%)  3
Pain  1  2/35 (5.71%)  2 1/33 (3.03%)  1
Rigors  1  2/35 (5.71%)  2 0/33 (0.00%)  0
Infections and infestations     
Infection  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Infection without neutropenia  1  8/35 (22.86%)  12 2/33 (6.06%)  4
Investigations     
Aspartate aminotransferase increased  1  1/35 (2.86%)  1 0/33 (0.00%)  0
CD4 lymphocytes decreased  1  1/35 (2.86%)  3 0/33 (0.00%)  0
CPK (creatine phosphokinase)  1  0/35 (0.00%)  0 1/33 (3.03%)  3
Creatinine  1  0/35 (0.00%)  0 2/33 (6.06%)  2
Leukopenia  1  3/35 (8.57%)  13 0/33 (0.00%)  0
Lymphopenia  1  2/35 (5.71%)  12 1/33 (3.03%)  1
Neutropenia  1  13/35 (37.14%)  59 2/33 (6.06%)  6
Prothrombin Time  1  1/35 (2.86%)  1 1/33 (3.03%)  1
Metabolism and nutrition disorders     
Hyperglycemia  1  2/35 (5.71%)  4 0/33 (0.00%)  0
Hypocalcemia  1  0/35 (0.00%)  0 1/33 (3.03%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Bone pain  1  0/35 (0.00%)  0 2/33 (6.06%)  2
Musculoskeletal  1  1/35 (2.86%)  2 0/33 (0.00%)  0
Myalgia  1  1/35 (2.86%)  1 2/33 (6.06%)  2
Nervous system disorders     
Ataxia  1  2/35 (5.71%)  2 0/33 (0.00%)  0
Depressed level of consciousness  1  18/35 (51.43%)  48 1/33 (3.03%)  1
Dizziness  1  2/35 (5.71%)  2 1/33 (3.03%)  1
Headache  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Ischemia-Cerebral  1  1/35 (2.86%)  1 1/33 (3.03%)  1
Neuro-Cranial  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Peripheral motor neuropathy  1  4/35 (11.43%)  5 0/33 (0.00%)  0
Peripheral sensory neuropathy  1  28/35 (80.00%)  304 6/33 (18.18%)  10
Seizure  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Syncope  1  3/35 (8.57%)  5 0/33 (0.00%)  0
Tremor  1  1/35 (2.86%)  3 1/33 (3.03%)  1
Vasovagal Episode  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Psychiatric disorders     
Depression  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Insomnia  1  0/35 (0.00%)  0 1/33 (3.03%)  1
Renal and urinary disorders     
Ureteral Obstruction  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  1/35 (2.86%)  1 0/33 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash/Desquamation  1  10/35 (28.57%)  24 8/33 (24.24%)  10
Rash/dermatitis associated with high-dose chemotherapy or BMT studies.  1  0/35 (0.00%)  0 1/33 (3.03%)  1
Vascular disorders     
Thrombosis  1  1/35 (2.86%)  1 1/33 (3.03%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 5
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Thomas Witzig
Organization: Mayo Clinic
EMail: witzig@mayo.edu
Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00432458     History of Changes
Other Study ID Numbers: CDR0000530050
P30CA015083 ( U.S. NIH Grant/Contract )
MC0289 ( Other Identifier: Mayo Clinic Cancer Center )
421-03 ( Other Identifier: Mayo Clinic IRB )
First Submitted: February 5, 2007
First Posted: February 7, 2007
Results First Submitted: April 11, 2012
Results First Posted: July 4, 2012
Last Update Posted: July 4, 2012