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

Brief Summary

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.

  • Study Type: Interventional
  • Study Design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: December 2009

Detailed Clinical Trial 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 Used in this Clinical Trial

  • Biological: Anakinra (IL-1Ra)
    • 100mg daily subcutaneously administered
  • Drug: 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)

Arms, Groups and Cohorts in this Clinical Trial

  • 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.

Outcome Measures for this Clinical Trial

Primary 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
    • Time Frame: 6 months
      Safety Issue?: No

Secondary Measures

  • Number of Patients With Response to Treatment With Dexamethasone and Anakinra
    • Time Frame: During Active treatment (up to 5 years)
      Safety Issue?: No
  • Number of Patients Who Are Progression-free and Alive at 6 Months
    • Time Frame: at 6 months
      Safety Issue?: No
  • 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)
      Safety Issue?: Yes
  • 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)
      Safety Issue?: No
  • 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)
      Safety Issue?: Yes
  • Duration of Response
    • Time Frame: From first documentation of response to progression or last follow-up (up to 5 years)
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Mayo Clinic
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • John A. Lust, M.D., Mayo Clinic
  • Overall Official(s)
    • John A. Lust, MD, PhD, Principal Investigator, Mayo Clinic

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00635154