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

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary * Determine the response rate in patients with smoldering or indolent multiple myeloma treated with anakinra. Secondary Determine the toxicity of anakinra alone or in combination with dexamethasone in these patients. Evaluate the response rate in patients treated with anakinra in combination with dexamethasone. Evaluate the proportion of patients who are progression-free at 6 months. Determine the tolerability of anakinra in combination with dexamethasone in these patients. Determine the time to progression to active multiple myeloma in patients treated with anakinra alone or in combination with dexamethasone. Assess the duration of response in these patients. OUTLINE: Induction therapy: Patients receive anakinra subcutaneously (SC) once daily for 6 months (months 1-6). Based on response, patients continue on treatment in one of three ways. Complete response [CR], very good partial response [VGPR], partial response [PR], or minimal response [MR]: Patients continue to receive anakinra SC once daily for 6 additional months (months 7-12). Patients who develop disease progression at anytime proceed to treatment with high dose dexamethasone. Stable disease: Patients receive low-dose oral dexamethasone once weekly for 6 months (months 7-12) with anakinra SC once daily. Patients who maintain stable disease or responded will continue low-dose oral dexamethasone and anakinra SC once daily for 6 additional months (months 13-18). Patients who develop disease progression at any time proceed to treatment with high dose dexamethasone. Progressive disease: Patients receive high-dose oral dexamethasone on days 1-4, 9-12, and 17-20 in months 7, 9, and 11 and on days 1-4 in months 8, 10, and 12 with anakinra SC once daily for 6 additional months (months 7-12). 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.

Official Title
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A Phase II Study of Anakinra (IL-1 Receptor Antagonist) in Patients With Smoldering/Indolent Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: Anakinra (IL-1Ra)
* Drug: Dexamethasone acetate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: New or preexisting diagnosis of multiple myeloma - Smoldering or indolent multiple myeloma meeting one of the following criteria: Bone marrow plasma cells ≥ 10% Serum monoclonal IgG or IgA protein ≥ 3.0 g/dL OR urine monoclonal light chain ≥ 1g by 24-hour urine protein electrophoresis 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra with/without Dexamethasone<br>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. | Biological: Anakinra (IL-1Ra)<br>* 100mg daily subcutaneously administered<br>Drug: Dexamethasone acetate<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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: 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 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma