Lenalidomide and Dexamethasone With or Without Anakinra in Treating Patients With Early Stage Multiple Myeloma

NCT02492750 | Completed Phase 1 Results DMC

• 4 other identifiers: MC138BNCI-2015-01041RV-CL-MM-PI-004334P30CA015083
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of anakinra when given together with lenalidomide and dexamethasone in treating patients with early stage multiple myeloma. Biological therapies, such as lenalidomide and anakinra, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether lenalidomide and dexamethasone are more effective with or without anakinra in treating patients with multiple myeloma.

Conditions

Indolent Plasma Cell Myeloma; Plasma Cell Myeloma; Smoldering Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing a Dose-limiting Toxicity (DLT)

  Number of participants experiencing a dose-limiting toxicity (DLT) is reported below. Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  28 days

• Number of Participants Who Experienced at Least One Grade 3+ Adverse Events Deemed at Least Possibly Related to Treatment, Graded According to NCI CTCAE Version 4.0

  The number of participants who experienced at least one grade 3+ adverse events deemed at least possibly related to treatment, graded according to NCI CTCAE version 4.0, is reported below.

  Up to 41 months

• Best Response

  The following response terms will be used: stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), Minimal Response (MR), stable disease (SD), and progressive disease (PD). The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy. PR defined as: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24hrs; ≥ 50% reduction in the size of soft tissue plasmacytomas. MR defined as: ≥25% but ≤ 49% reduction of serum M protein and reduction in 24-hour urine M-protein by 50-89% which still exceeds 200mg/24 hours; 25-49% reduction in the size of soft tissue plasmacytoma and No increase in the size or number of lytic bone lesions. VGPR defined as: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein \<100 mg/24 h

  Up to 41 months

Study Arms (2)

Arm A (lenalidomide, dexamethasone, anakinra)

EXPERIMENTAL

Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Biological: Anakinra; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide

Arm B (lenalidomide, dexamethasone, placebo)

ACTIVE COMPARATOR

Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Other: Placebo

Interventions

Anakinra BIOLOGICAL

Given SC

Also known as: Kinaret, Kineret, rIL-1ra, rIL1RN

Arm A (lenalidomide, dexamethasone, anakinra)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Arm A (lenalidomide, dexamethasone, anakinra); Arm B (lenalidomide, dexamethasone, placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (lenalidomide, dexamethasone, anakinra); Arm B (lenalidomide, dexamethasone, placebo)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Arm A (lenalidomide, dexamethasone, anakinra); Arm B (lenalidomide, dexamethasone, placebo)

Placebo OTHER

Given SC

Also known as: placebo therapy, PLCB, sham therapy

Arm B (lenalidomide, dexamethasone, placebo)

Eligibility Criteria

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

You may qualify if:

• Absolute neutrophil count (ANC) \>= 1700/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \>= 8.0 g/dL
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 x upper limit of normal (ULN)
• Creatinine clearance \>= 30 mL/min (as determined by Cockroft-Gault equation)
• Diagnosis of multiple myeloma according to International Myeloma Working Group criteria and one of the following:
• Smoldering multiple myeloma (SMM)
• Indolent multiple myeloma (IMM)
• Newly diagnosed multiple myeloma (MM)
• Note: patients with lytic disease and anemia are eligible
• High risk disease defined by all of the following:
• \>= 10% bone marrow plasma cells AND
• Abnormal serum free light chain (FLC) ratio (\< 0.26 or \> 1.65) by serum FLC assay AND
• Monotypic plasma cell S-phase \>= 0.3%
• Measurable level of M-protein \> 1 g/dL on serum protein electrophoresis or \> 200 mg of M-protein on a 24 hour urine protein electrophoresis

You may not qualify if:

• Prior treatment with any other agent that may affect M-protein =\< 30 days prior to registration
• Acute/chronic infections, open wounds, or any active infection requiring intravenous antibiotic therapy =\< 12 weeks prior to registration
• Other active malignancy (=\< 3 years) prior to registration; exceptions: basal cell skin cancer or carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy
• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• New York Heart Association (NYHA) class 3 or 4 congestive heart failure (CHF) symptoms
• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are allowed while on protocol treatment

Sponsors & Collaborators

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

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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; Precancerous Conditions; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: John A Lust MD PhD
• Organization: Mayo Clinic

lustj@mayo.edu

507/284-2511

Study Officials

• John Lust

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 9, 2015
• Study Start: April 1, 2016
• Primary Completion: June 5, 2019
• Study Completion: September 13, 2019
• Last Updated: March 25, 2020
• Results First Posted: March 25, 2020

Record last verified: 2019-06

Locations

US (1)