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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA015083 | U.S. NIH Grant/Contract | View source | |
| MC0282 | Other Identifier | Mayo Clinic Cancer Center | |
| 1316-02 | Other Identifier | Mayo Clinic IRB |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
RATIONALE: Some cancers need growth factors which are made by the body's white blood cells to keep growing.Anakinra may interfere with the growth factor and stop multiple myeloma from growing. Dexamethasone may stop cancer cells from growing. Giving anakinra together with dexamethasone may be an effective treatment for multiple myeloma.
PURPOSE: This phase II trial is studying how well anakinra works when given with or without dexamethasone in treating patients with smoldering myeloma or indolent multiple myeloma.
OBJECTIVES:
Primary
* Determine the response rate in patients with smoldering or indolent multiple myeloma treated with anakinra.
Secondary
OUTLINE:
NOTE: Patients may continue on treatment beyond 12 months at treating physician discretion.
After completion of study treatment, patients are followed every 6 months for up to 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anakinra with/without Dexamethasone | Experimental | Anakinra was given alone for 6 months at which time response was assessed. If participants achieved a minor response or better they continued on Anakinra alone until disease progression. If participants achieved stable disease, they added low dose Dexamethasone to Anakinra until progression. If at any time a participant progresses, they were administered high dose Dexamethasone with Anakinra. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anakinra (IL-1Ra) | Biological | 100mg daily subcutaneously administered |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Response Definitions:
| 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Response to Treatment With Dexamethasone and Anakinra | 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. | During Active treatment (up to 5 years) |
| Number of Patients Who Are Progression-free and Alive at 6 Months |
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DISEASE CHARACTERISTICS:
New or preexisting diagnosis of multiple myeloma
- Smoldering or indolent multiple myeloma meeting one of the following criteria:
Measurable disease
Does not require immediate chemotherapy, in the opinion of the treating physician
No active myeloma or primary amyloidosis requiring chemotherapy or any agents that may interact with anakinra (e.g., etanercept, infliximab, or thalidomide)
PATIENT CHARACTERISTICS:
Eastern Cooperative Oncology Group (ECOG) performance status 0
Total WBC ≥ 3,500/mm^3
ANC ≥ 1,700/mm^3
Creatinine ≤ 1.5 times upper limit of normal
Able to self-inject medication or have a caregiver who can administer the drug
Not pregnant or nursing
Negative pregnancy test
No acute or chronic infections, open wounds, or any active infection requiring intravenous antibiotic therapy within the past 12 weeks
No active malignancy within the past 5 years except basal cell carcinoma of the skin or carcinoma in situ of cervix
- Patients with a previously resected malignancy that does not require further treatment are eligible
No New York Heart Association (NYHA) class III or IV congestive heart failure
No rheumatoid arthritis or other diseases requiring immunosuppressive therapy
No asthma, inflammatory bowel disease, or any debilitating physical or psychiatric illness that, in the judgment of the investigator, would interfere with the conduct of the study
PRIOR CONCURRENT THERAPY:
* More than 30 days since prior treatment with dehydroepiandrosterone (DHEA), clarithromycin, pamidronate, steroids, or any other agent that may affect M-protein
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| Name | Affiliation | Role |
|---|---|---|
| John A. Lust, MD, PhD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26945843 | Derived | Lust JA, Lacy MQ, Zeldenrust SR, Witzig TE, Moon-Tasson LL, Dinarello CA, Donovan KA. Reduction in C-reactive protein indicates successful targeting of the IL-1/IL-6 axis resulting in improved survival in early stage multiple myeloma. Am J Hematol. 2016 Jun;91(6):571-4. doi: 10.1002/ajh.24352. Epub 2016 Apr 13. | |
| 19181644 | Derived | Lust JA, Lacy MQ, Zeldenrust SR, Dispenzieri A, Gertz MA, Witzig TE, Kumar S, Hayman SR, Russell SJ, Buadi FK, Geyer SM, Campbell ME, Kyle RA, Rajkumar SV, Greipp PR, Kline MP, Xiong Y, Moon-Tasson LL, Donovan KA. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1beta-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc. 2009 Feb;84(2):114-22. doi: 10.4065/84.2.114. |
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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).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Anakinra With/Without Dexamethasone |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Anakinra With/Without Dexamethasone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Response Definitions:
| Participants who met the eligibility criteria, signed the consent form and have began treatment were considered evaluable. | Posted | Number | participants | 6 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Anakinra With/Without Dexamethasone |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 5 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 5 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John Lust | Mayo Clinic | lust.john@mayo.edu |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D053590 | Interleukin 1 Receptor Antagonist Protein |
| C018038 | dexamethasone acetate |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Dexamethasone acetate | Drug | Low dose - 20 mg/week High dose - 40mg days 1-4, 9-12, 17-20 every 28 days ODD cycles OR 40 mg days 1-4 every 28 days EVEN cycles. (Starting dose was determined by treating physician) |
|
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:
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. |
| at 6 months |
| Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone. | 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. | Duration of treatment (up to 5 years) |
| Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone | 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 from registration to progression or death (up to 5 years) |
| Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone | 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. | every cycle during treatment (up to 5 years) |
| Duration of Response | 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. | From first documentation of response to progression or last follow-up (up to 5 years) |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Diagnosis | Number | participants |
|
| Prior treatment for M-protein | Number | participants |
|
Patients in this outcome received only Anakinra (100mg daily subcutaneously administered). |
|
|
|
| Secondary | Number of Patients With Response to Treatment With Dexamethasone and Anakinra | 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. | Only participants who received Anakinra with dexamethasone were analyzed. | Posted | Number | participants | During Active treatment (up to 5 years) |
|
|
|
| Secondary | Number of Patients Who Are Progression-free and Alive at 6 Months | 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:
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. | Posted | Number | participants | at 6 months |
|
|
|
| Secondary | Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone. | 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. | Posted | Number | participants | Duration of treatment (up to 5 years) |
|
|
|
| Secondary | Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone | 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. | PFS results were published in Mayo Clin Proc, Feb 2009. 47 patients were analyzed for this publication. | Posted | Median | 95% Confidence Interval | months | Time from registration to progression or death (up to 5 years) |
|
|
|
| Secondary | Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone | 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. | Only participants who received Anakinra with low or high dose dexamethasone were analyzed. | Posted | Number | participants | every cycle during treatment (up to 5 years) |
|
|
|
| Secondary | Duration of Response | 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. | Participants (receiving Anakinra alone or in combination with Dexamethasone) who achieved a MR or better were analyzed. | Posted | Median | 95% Confidence Interval | months | From first documentation of response to progression or last follow-up (up to 5 years) |
|
|
|
| 8 |
| 54 |
| 53 |
| 54 |
| Supraventricular arrhythmias (SVT/atrial fibrillation/flutter) | Cardiac disorders | MedDRA 5 | Systematic Assessment |
|
| Infection without neutropenia | Infections and infestations | MedDRA 5 | Systematic Assessment |
|
| Neutropenia | Investigations | MedDRA 5 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 5 | Systematic Assessment |
|
| Hemorrhage | Vascular disorders | MedDRA 5 | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 5 | Systematic Assessment |
|
| Anemia-Leukemia | Blood and lymphatic system disorders | MedDRA 5 | Systematic Assessment |
|
| Cardiovascular | Cardiac disorders | MedDRA 5 | Systematic Assessment |
|
| Edema | Cardiac disorders | MedDRA 5 | Systematic Assessment |
|
| Ischemia/Infarction | Cardiac disorders | MedDRA 5 | Systematic Assessment |
|
| Left ventricular failure | Cardiac disorders | MedDRA 5 | Systematic Assessment |
|
| Supraventricular arrhythmias (SVT/atrial fibrillation/flutter) | Cardiac disorders | MedDRA 5 | Systematic Assessment |
|
| Middle Ear | Ear and labyrinth disorders | MedDRA 5 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 5 | Systematic Assessment |
|
| Vision-Blurred | Eye disorders | MedDRA 5 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 5 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 5 | Systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 5 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 5 | Systematic Assessment |
|
| Oral cavity Mucositis/stomatitis (functional/symptomatic) | Gastrointestinal disorders | MedDRA 5 | Systematic Assessment |
|
| Pain-Abdominal | Gastrointestinal disorders | MedDRA 5 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 5 | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA 5 | Systematic Assessment |
|
| Pain-Chest | General disorders | MedDRA 5 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 5 | Systematic Assessment |
|
| Infection without neutropenia | Infections and infestations | MedDRA 5 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 5 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 5 | Systematic Assessment |
|
| Creatinine | Investigations | MedDRA 5 | Systematic Assessment |
|
| GGT (Gamma-Glutamyl transpeptidase) | Investigations | MedDRA 5 | Systematic Assessment |
|
| Leukopenia | Investigations | MedDRA 5 | Systematic Assessment |
|
| Neutropenia | Investigations | MedDRA 5 | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | MedDRA 5 | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 5 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 5 | Systematic Assessment |
|
| Muscle Weakness | Musculoskeletal and connective tissue disorders | MedDRA 5 | Systematic Assessment |
|
| Musculoskeletal | Musculoskeletal and connective tissue disorders | MedDRA 5 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 5 | Systematic Assessment |
|
| Confusion | Psychiatric disorders | MedDRA 5 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 5 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 5 | Systematic Assessment |
|
| Dyruria | Renal and urinary disorders | MedDRA 5 | Systematic Assessment |
|
| Adult respiratory distress syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | MedDRA 5 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 5 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 5 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 5 | Systematic Assessment |
|
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| D002318 |
| Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D011506 | Proteins |
| D001685 | Biological Factors |