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

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Anakinra (IL-1Ra)
Dexamethasone acetate
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anakinra with/without Dexamethasone

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 12, 2008
Last Updated
May 8, 2018
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00635154
Brief Title
Anakinra With or Without Dexamethasone in Treating Patients With Smoldering or Indolent Multiple Myeloma
Official Title
A Phase II Study of Anakinra (IL-1 Receptor Antagonist) in Patients With Smoldering/Indolent Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2010
Overall Recruitment Status
Completed
Study Start Date
December 2002 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anakinra with/without Dexamethasone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Anakinra (IL-1Ra)
Intervention Description
100mg daily subcutaneously administered
Intervention Type
Drug
Intervention Name(s)
Dexamethasone acetate
Intervention Description
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)
Primary Outcome Measure Information:
Title
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
Description
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
Secondary Outcome Measure Information:
Title
Number of Patients With Response to Treatment With Dexamethasone and Anakinra
Description
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)
Title
Number of Patients Who Are Progression-free and Alive at 6 Months
Description
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
Title
Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone.
Description
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)
Title
Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone
Description
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)
Title
Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone
Description
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)
Title
Duration of Response
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John A. Lust, MD, PhD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26945843
Citation
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.
Results Reference
derived
PubMed Identifier
19181644
Citation
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.
Results Reference
derived

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

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