Multiple Myeloma and Plasma Cell NeoplasmPhase 2NCT00635154
Anakinra With or Without Dexamethasone in Treating Patients With Smoldering or Indolent Multiple Myeloma
A Phase 2 study testing Anakinra (IL-1Ra) and Dexamethasone acetate in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- Anakinra (IL-1Ra) and Dexamethasone acetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2002to Nov 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Anakinra (IL-1 Receptor Antagonist) in Patients With Smoldering/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.
Read the 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.
- Being tested
- Anakinra (IL-1Ra), Dexamethasone acetate
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anakinra (IL-1Ra)Biological
100mg daily subcutaneously administered
Dexamethasone acetateDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Anakinra (IL-1Ra); Drug: Dexamethasone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From first documentation of response to progression or last follow-up (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startDec 2002
- Primary completionDec 2009
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- John A. Lust, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00635154
- Sponsor's protocol ID
- CDR0000583300
- Other IDs
- P30CA015083, MC0282, 1316-02
- Status last verified
- Dec 2010
- First submitted
- 12 Mar 2008
- Last updated
- 7 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 26945843Lust 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.
PubMed 19181644
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Anakinra (IL-1 Receptor Antagonist) in Patients With Smoldering/Indolent Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00635154
- Acronym / sponsor ID
- CDR0000583300
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2002
- Primary completion
- Dec 2009 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 9 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anakinra with/without Dexamethasone | Experimental | Biological: Anakinra (IL-1Ra), Drug: Dexamethasone acetateAnakinra 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. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anakinra (IL-1Ra)100mg daily subcutaneously administered | Biological | Anakinra with/without Dexamethasone |
| Dexamethasone acetateLow 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) | Drug | Anakinra with/without Dexamethasone |
Primary outcome
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
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 secondary outcomes
Number of Patients With Response to Treatment With Dexamethasone and Anakinra
Time frame: During Active treatment (up to 5 years)
Number of Patients Who Are Progression-free and Alive at 6 Months
Time frame: at 6 months
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)
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)
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)
Duration of Response
Time frame: From first documentation of response to progression or last follow-up (up to 5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26945843Lust 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.
- Derived from this study: PubMed 19181644Lust 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John A. Lust, MD, PhD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra (IL-1Ra) and Dexamethasone acetate in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00635154, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2018; AzTrials last refreshed its copy on 6 Nov 2026.