Anakinra With or Without Dexamethasone in Treating Patients With Smoldering or Indolent Multiple Myeloma
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.
Multiple Myeloma and Plasma Cell Neoplasm
Biological: Anakinra (IL-1Ra)
Drug: Dexamethasone acetate
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Anakinra (IL-1 Receptor Antagonist) in Patients With Smoldering/Indolent Multiple Myeloma|
- 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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
- Number of Patients With Response to Treatment With Dexamethasone and Anakinra [ Time Frame: During Active treatment (up to 5 years) ] [ Designated as safety issue: No ]
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.
- Number of Patients Who Are Progression-free and Alive at 6 Months [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
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.
- Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone. [ Time Frame: Duration of treatment (up to 5 years) ] [ Designated as safety issue: Yes ]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.
- Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone [ Time Frame: Time from registration to progression or death (up to 5 years) ] [ Designated as safety issue: No ]
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.
- Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone [ Time Frame: every cycle during treatment (up to 5 years) ] [ Designated as safety issue: Yes ]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 Response [ Time Frame: From first documentation of response to progression or last follow-up (up to 5 years) ] [ Designated as safety issue: No ]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.
|Study Start Date:||December 2002|
|Study Completion Date:||November 2010|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Experimental: Anakinra with/without Dexamethasone
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)
100mg daily subcutaneously administeredDrug: Dexamethasone acetate
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)
* Determine the response rate in patients with smoldering or indolent multiple myeloma treated with anakinra.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00635154
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||John A. Lust, MD, PhD||Mayo Clinic|