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Anakinra With or Without Dexamethasone in Treating Patients With Smoldering or Indolent Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00635154
Recruitment Status : Completed
First Posted : March 13, 2008
Results First Posted : December 9, 2010
Last Update Posted : June 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma and Plasma Cell Neoplasm
Interventions Biological: Anakinra (IL-1Ra)
Drug: Dexamethasone acetate
Enrollment 55
Recruitment Details

55 patients were recruited from November 2002 through December 2007 at Mayo Clinic.

One patient had progressive disease prior to starting treatment. This patient was excluded from all analysis.

Pre-assignment Details Patients received induction therapy of Anakinra alone for 6 months. Based on response, dexamethasone could be added or increased in subsequent cycles. See the Outline section for more detail. Unless otherwise stated, results are reported for all patients (regardless of dexamethasone administration).
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description [Not Specified]
Period Title: Overall Study
Started 54
Completed 21
Not Completed 33
Reason Not Completed
Alternative Treatment             8
Other             4
Still on treatment             21
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 54 participants
60.0
(38 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants
Female
25
  46.3%
Male
29
  53.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 54 participants
54
Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 54 participants
Smoldering Multiple Myeloma (SMM) 44
Indolent Multiple Myeloma (IMM) 10
Prior treatment for M-protein  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 54 participants
Yes 10
No 44
1.Primary Outcome
Title Patients With Confirmed Response (Complete Response, Very Good Partial Response, Partial Response, or Minimal Response) on 2 Consecutive Months During the First 6 Months of Treatment With Anakinra Alone
Hide Description

Response Definitions:

  • Complete Response(CR):disappearance of M-Protein from serum & urine and immunofixation, <5% bone marrow(BM) plasma cells & disappearance of soft tissue plasmacytomas(STP);
  • Very Good Partial Response(VGPR):>=90% decrease in serum M-Protein, Urine M-protein <100 mg/24 hours, <=5% BM plasma cells, disappearance of STP;
  • Partial response(PR):>=50% reduction in serum M-protein, >=90% decrease in Urine M-protein or <200 mg/24 hours & >=50% decrease in STP;
  • Minor response(MR):25-49% decrease in serum M-protein, 50-89% decrease in urine M-protein & 25-49% decrease in STP
Time Frame 6 months
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Hide Analysis Population Description
Participants who met the eligibility criteria, signed the consent form and have began treatment were considered evaluable.
Arm/Group Title Anakinra Without Dexamethasone
Hide Arm/Group Description:
Patients in this outcome received only Anakinra (100mg daily subcutaneously administered).
Overall Number of Participants Analyzed 54
Measure Type: Number
Unit of Measure: participants
1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anakinra Without Dexamethasone
Comments Proportion of confirmed responses to Anakinra alone was estimated by the number of patients who achieved a confirmed response divided by the total number of assessable patients.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Proportion of confirmed responses (%)
Estimated Value 1.8
Confidence Interval 95%
0.5 to 10
Estimation Comments 95% Confidence intervals were calculated for the true confirmed response rate using properties of the binomial distribution.
2.Secondary Outcome
Title Number of Patients With Response to Treatment With Dexamethasone and Anakinra
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Response on 2 consecutive months during active treatment with anakinra alone or in combination with dexamethasone.

Response criteria is the same as in Primary Outcome Measure.

Time Frame During Active treatment (up to 5 years)
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Hide Analysis Population Description
Only participants who received Anakinra with dexamethasone were analyzed.
Arm/Group Title Anakinra With Dexamethasone
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Patients in this outcome received both Anakinra (100mg daily subcutaneously administered) and dexamethasone (either 20mg/week OR 40mg days 1-4, 9-12, 17-20 every 28 days during odd cycles OR 40 mg days 1-4 every 28 days during even cycles)
Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: participants
14
3.Secondary Outcome
Title Number of Patients Who Are Progression-free and Alive at 6 Months
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Disease stability was assessed by evaluating the proportion of participants who are progression free (and alive) at 6 months.

Progression was defined as any one or more of the following:

An increase of 25% from lowest confirmed response:

  • Serum M-component (absolute increase >=1.0 g/dL)
  • Urine M-component (absolute increase >=200 mg/24 hours)

An increase of 50% above the lowest remission value in bone marrow plasmacytosis (absolute increase 25% bone marrow plasma cells)

Development of new bone lesions or soft tissue plasmacytomas.

Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 54
Measure Type: Number
Unit of Measure: participants
49
4.Secondary Outcome
Title Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone.
Hide Description Severe non-hematologic adverse events were defined as adverse events grade 4 (life threatening or disabling) or grade 5 (death), regardless of attribution to study drug. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) version 2.
Time Frame Duration of treatment (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 54
Measure Type: Number
Unit of Measure: participants
7
5.Secondary Outcome
Title Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone
Hide Description

PFS was defined as the time from registration to progression or death due to any cause.

Progression is defined the same as outcome measure #3.

Time Frame Time from registration to progression or death (up to 5 years)
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Hide Analysis Population Description
PFS results were published in Mayo Clin Proc, Feb 2009. 47 patients were analyzed for this publication.
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 47
Median (95% Confidence Interval)
Unit of Measure: months
37.5 [1] 
(9.6 to NA)
[1]
The upper bound for the confidence interval has not been attained.
6.Secondary Outcome
Title Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone
Hide Description Severe non-hematologic adverse events were defined as adverse events grade 4 (life threatening or disabling) or grade 5 (death), regardless of attribution to study drug. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) version 2.
Time Frame every cycle during treatment (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants who received Anakinra with low or high dose dexamethasone were analyzed.
Arm/Group Title Anakinra With Dexamethasone
Hide Arm/Group Description:
Patients in this outcome received both Anakinra (100mg daily subcutaneously administered) and dexamethasone (either 20mg/week OR 40mg days 1-4, 9-12, 17-20 every 28 days during odd cycles OR 40 mg days 1-4 every 28 days during even cycles)
Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: participants
4
7.Secondary Outcome
Title Duration of Response
Hide Description Duration of response is defined for all evaluable participants (receiving Anakinra alone or in combination with Dexamethasone) who have achieved an objective response as the date at which the participants status was first noted to be MR or better to the date progression is documented or the date of last follow-up.
Time Frame From first documentation of response to progression or last follow-up (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants (receiving Anakinra alone or in combination with Dexamethasone) who achieved a MR or better were analyzed.
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: months
41.9 [1] 
(14.6 to NA)
[1]
The upper bound for the confidence interval has not been attained.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Anakinra With/Without Dexamethasone
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Anakinra With/Without Dexamethasone
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Anakinra With/Without Dexamethasone
Affected / at Risk (%) # Events
Total   8/54 (14.81%)    
Blood and lymphatic system disorders   
Anemia  1  1/54 (1.85%)  1
Cardiac disorders   
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)  1  1/54 (1.85%)  1
Infections and infestations   
Infection without neutropenia  1  2/54 (3.70%)  2
Investigations   
Neutropenia  1  1/54 (1.85%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumonitis  1  2/54 (3.70%)  2
Vascular disorders   
Hemorrhage  1  2/54 (3.70%)  2
Thrombosis  1  3/54 (5.56%)  4
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%
Anakinra With/Without Dexamethasone
Affected / at Risk (%) # Events
Total   53/54 (98.15%)    
Blood and lymphatic system disorders   
Anemia  1  3/54 (5.56%)  5
Anemia-Leukemia  1  1/54 (1.85%)  1
Cardiac disorders   
Cardiovascular  1  1/54 (1.85%)  1
Edema  1  10/54 (18.52%)  19
Ischemia/Infarction  1  1/54 (1.85%)  1
Left ventricular failure  1  1/54 (1.85%)  1
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)  1  2/54 (3.70%)  2
Ear and labyrinth disorders   
Middle Ear  1  1/54 (1.85%)  1
Eye disorders   
Cataract  1  2/54 (3.70%)  2
Vision-Blurred  1  5/54 (9.26%)  6
Gastrointestinal disorders   
Colitis  1  1/54 (1.85%)  1
Dyspepsia  1  16/54 (29.63%)  27
Gastrointestinal disorder  1  1/54 (1.85%)  1
Nausea  1  1/54 (1.85%)  1
Oral cavity Mucositis/stomatitis (functional/symptomatic)  1  2/54 (3.70%)  2
Pain-Abdominal  1  1/54 (1.85%)  1
General disorders   
Fatigue  1  4/54 (7.41%)  4
Injection site reaction  1  46/54 (85.19%)  92
Pain-Chest  1  1/54 (1.85%)  1
Immune system disorders   
Hypersensitivity  1  3/54 (5.56%)  3
Infections and infestations   
Infection without neutropenia  1  32/54 (59.26%)  89
Investigations   
Alanine aminotransferase increased  1  1/54 (1.85%)  1
Aspartate aminotransferase increased  1  1/54 (1.85%)  1
Creatinine  1  13/54 (24.07%)  53
GGT (Gamma-Glutamyl transpeptidase)  1  1/54 (1.85%)  1
Leukopenia  1  24/54 (44.44%)  140
Neutropenia  1  36/54 (66.67%)  236
Metabolism and nutrition disorders   
Hypercalcemia  1  2/54 (3.70%)  2
Hyperglycemia  1  22/54 (40.74%)  94
Musculoskeletal and connective tissue disorders   
Bone pain  1  1/54 (1.85%)  1
Muscle Weakness  1  3/54 (5.56%)  7
Musculoskeletal  1  1/54 (1.85%)  1
Psychiatric disorders   
Anxiety  1  12/54 (22.22%)  27
Confusion  1  1/54 (1.85%)  1
Depression  1  1/54 (1.85%)  1
Insomnia  1  10/54 (18.52%)  23
Renal and urinary disorders   
Dyruria  1  1/54 (1.85%)  1
Respiratory, thoracic and mediastinal disorders   
Adult respiratory distress syndrome (ARDS)  1  1/54 (1.85%)  1
Cough  1  1/54 (1.85%)  1
Dyspnea  1  1/54 (1.85%)  1
Pneumonitis  1  1/54 (1.85%)  1
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. John Lust
Organization: Mayo Clinic
EMail: lust.john@mayo.edu
Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00635154     History of Changes
Other Study ID Numbers: CDR0000583300
P30CA015083 ( U.S. NIH Grant/Contract )
MC0282 ( Other Identifier: Mayo Clinic Cancer Center )
1316-02 ( Other Identifier: Mayo Clinic IRB )
First Submitted: March 12, 2008
First Posted: March 13, 2008
Results First Submitted: November 9, 2010
Results First Posted: December 9, 2010
Last Update Posted: June 7, 2018