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

Condition(s) targeted: Multiple Myeloma and Plasma Cell Neoplasm

Intervention: anakinra (Drug); dexamethasone (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
John A. Lust, MD, PhD, Principal Investigator, Affiliation: Mayo Clinic

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.

Official title: A Phase II Study of Anakinra (IL-1 Receptor Antagonist) in Patients With Smoldering/Indolent Multiple Myeloma

Study design: Treatment, Open Label

Primary outcome: Confirmed response (complete response, very good partial response, partial response, or minimal response) after treatment with anakinra alone

Secondary outcome:

Response rate after treatment with dexamethasone and anakinra

Progression-free survival at 6 months

Duration of response

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).

Patients are then assigned to 1 of 3 treatment groups according to their response to induction therapy.

- Group 1 (complete response [CR], very good partial response [VGPR], partial response

[PR], minimal response [MR], or stable disease): Patients continue to receive anakinra SC once daily for 6 additional months (months 7-12)*. Patients who develop disease progression proceed to treatment in group 3.

- Group 2 (stable disease): Patients receive low-dose oral dexamethasone once weekly for 6

months (months 7-12). Patients who develop disease progression proceed to treatment in group 3. Patients who maintain stable disease or who achieve CR, VGPR, PR, or MR continue to receive low-dose oral dexamethasone once weekly for 6 additional months (months 13-18) and anakinra SC once daily for 6 additional months (months 13-18)*. Patients who develop disease progression proceed to treatment in group 3.

- Group 3 (progressive disease): Patients continue to receive anakinra SC once daily for 6

additional months (months 7-12)*. Patients also receive high-dose oral dexamethasone once daily 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.

NOTE: *Patients may continue to receive anakinra at the physician's discretion.

After completion of study treatment, patients are followed periodically.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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:

- 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 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 judgement 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

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: November 2002
Last updated: May 23, 2008