Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
Brief summary
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
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.
Interventions
BIOLOGICALAnakinra (IL-1Ra)
100mg daily subcutaneously administered
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)
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Are Progression-free and Alive at 6 Months | 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. |
| Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone. | Duration of treatment (up to 5 years) | 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. |
| Number of Patients With Response to Treatment With Dexamethasone and Anakinra | During Active treatment (up to 5 years) | 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 With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone | every cycle during treatment (up to 5 years) | 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 | From first documentation of response to progression or last follow-up (up to 5 years) | 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. |
| Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone | Time from registration to progression or death (up to 5 years) | 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. |
Countries
United States
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| Anakinra With/Without Dexamethasone | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Alternative Treatment | 8 |
| Overall Study | Other | 4 |
| Overall Study | Still on treatment | 21 |
Baseline characteristics
| Characteristic | Anakinra With/Without Dexamethasone |
|---|---|
| Age, Continuous | 60.0 years |
| Diagnosis Indolent Multiple Myeloma (IMM) | 10 participants |
| Diagnosis Smoldering Multiple Myeloma (SMM) | 44 participants |
| Prior treatment for M-protein No | 44 participants |
| Prior treatment for M-protein Yes | 10 participants |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 53 / 54 |
| serious Total, serious adverse events | 8 / 54 |
Outcome results
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: * 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
Population: Participants who met the eligibility criteria, signed the consent form and have began treatment were considered evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anakinra Without Dexamethasone | 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 | 1 participants |
Comparison: 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.95% CI: [0.5, 10]
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.
Time frame: From first documentation of response to progression or last follow-up (up to 5 years)
Population: Participants (receiving Anakinra alone or in combination with Dexamethasone) who achieved a MR or better were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra Without Dexamethasone | Duration of Response | 41.9 months |
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: * 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anakinra Without Dexamethasone | Number of Patients Who Are Progression-free and Alive at 6 Months | 49 participants |
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.
Time frame: During Active treatment (up to 5 years)
Population: Only participants who received Anakinra with dexamethasone were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anakinra Without Dexamethasone | Number of Patients With Response to Treatment With Dexamethasone and Anakinra | 14 participants |
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.
Time frame: every cycle during treatment (up to 5 years)
Population: Only participants who received Anakinra with low or high dose dexamethasone were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anakinra Without Dexamethasone | Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone | 4 participants |
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.
Time frame: Duration of treatment (up to 5 years)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anakinra Without Dexamethasone | Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone. | 7 participants |
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.
Time frame: Time from registration to progression or death (up to 5 years)
Population: PFS results were published in Mayo Clin Proc, Feb 2009. 47 patients were analyzed for this publication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra Without Dexamethasone | Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone | 37.5 months |