Clinical trial NCT00635154: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-03-13
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
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
timeFrame: 6 months
Secondary outcomes:
measure: Number of Patients With Response to Treatment With Dexamethasone and Anakinra
timeFrame: During Active treatment (up to 5 years)
measure: Number of Patients Who Are Progression-free and Alive at 6 Months
timeFrame: at 6 months
measure: Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone.
timeFrame: Duration of treatment (up to 5 years)
measure: Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone
timeFrame: Time from registration to progression or death (up to 5 years)
measure: Number of Patients With Severe Non-hematological Adverse Events in Participants Receiving Anakinra in Combination With Dexamethasone
timeFrame: every cycle during treatment (up to 5 years)
measure: Duration of Response
timeFrame: From first documentation of response to progression or last follow-up (up to 5 years)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: John A. Lust, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.