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

NCT00635154 | Completed Phase 2 Results

• 4 other identifiers: CDR0000583300P30CA015083MC02821316-02
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (6)

• Number of Patients With Response to Treatment With Dexamethasone and Anakinra

  During Active treatment (up to 5 years)

• Number of Patients Who Are Progression-free and Alive at 6 Months

  at 6 months

• Number of Patients With Severe Non-hematological Adverse Events in Patients Receiving Anakinra Alone or in Combination With Dexamethasone.

  Duration of treatment (up to 5 years)

• Progression Free Survival (PFS) in Patients Treated With Anakinra Alone or in Combination With Dexamethasone

  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

  every cycle during treatment (up to 5 years)

Study Arms (1)

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.

Biological: Anakinra (IL-1Ra); Drug: Dexamethasone acetate

Interventions

Anakinra (IL-1Ra) BIOLOGICAL

100mg daily subcutaneously administered

Anakinra with/without Dexamethasone

Dexamethasone acetate DRUG

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)

Anakinra with/without Dexamethasone

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• 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.

  PMID: 26945843 DERIVED

• 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.

  PMID: 19181644 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Interleukin 1 Receptor Antagonist Protein; dexamethasone acetate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. John Lust
• Organization: Mayo Clinic

lust.john@mayo.edu

Study Officials

• John A. Lust, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2008
• First Posted: March 13, 2008
• Study Start: December 1, 2002
• Primary Completion: December 1, 2009
• Study Completion: November 1, 2010
• Last Updated: June 7, 2018
• Results First Posted: December 9, 2010

Record last verified: 2010-12

Locations

US (1)