Ixazomib Citrate, Lenalidomide, and Dexamethasone in Treating Patients With POEMS Syndrome

NCT02921893 | Completed Early Phase 1 DMC

• 3 other identifiers: MC1682NCI-2016-0142616-002976
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ixazomib citrate, lenalidomide, and dexamethasone work in treating patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, 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. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving ixazomib citrate, lenalidomide, and dexamethasone may work better in treating patients with POEMS syndrome.

Conditions

Plasmacytoma; POEMS Syndrome

Outcome Measures

Primary Outcomes (1)

• Rate of normalization of VEGF defined as VEGF value decreasing to below upper limit of normal (86 pg/mL)

  In each group, the rate of normalization of VEGF by 3 months (post-3 cycles) will be examined along with the prognostic factors for patients accrued to this study. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.

  Up to 3 months

Secondary Outcomes (5)

• Hematologic response rate

  Up to 3 months

• Hematologic response rate

  Up to 12 months

• Normalization of VEGF

  Up to 12 months

• Survival time

  Time from registration to death due to any cause, assessed up to 3 years

• Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 3 years

Other Outcomes (14)

• Change in peripheral neuropathy evaluated by Modified Neurological Impairment Score +7 polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes

  Baseline up to 36 months

• Change in positron emission tomography-scan

  3 months up to 36 months

• Change in presence or absence of ascites/effusions/edema

  3 months up to 36 months

Study Arms (2)

Group I (ixazomib citrate, lenalidomide, dexamethasone, ASCT)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15, lenalidomide PO QD on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care ASCT after completing 3 cycles of treatment.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Drug: Lenalidomide; Other: Questionnaire Administration

Group II (ixazomib citrate, lenalidomide, dexamethasone)

EXPERIMENTAL

Patients receive ixazomib citrate PO, lenalidomide PO QD, and dexamethasone PO as in Group I. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Drug: Lenalidomide; Other: Questionnaire Administration

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, 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, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Group I (ixazomib citrate, lenalidomide, dexamethasone, ASCT); Group II (ixazomib citrate, lenalidomide, dexamethasone)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Group I (ixazomib citrate, lenalidomide, dexamethasone, ASCT); Group II (ixazomib citrate, lenalidomide, dexamethasone)

Lenalidomide DRUG

Given PO

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

Group I (ixazomib citrate, lenalidomide, dexamethasone, ASCT); Group II (ixazomib citrate, lenalidomide, dexamethasone)

Questionnaire Administration OTHER

Ancillary studies

Group I (ixazomib citrate, lenalidomide, dexamethasone, ASCT); Group II (ixazomib citrate, lenalidomide, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• POEMS syndrome requiring therapy, previously treated or untreated
• Plasma vascular endothelial growth factor (VEGF) \> 2 x upper limit of normal (ULN)
• Presence of a plasma cell clone (any of the following):
• Monoclonal protein in the serum or urine
• Measurable light chains by free light chain assay
• Measurable plasmacytoma
• Monoclonal plasma cells in bone marrow
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2, or 3
• Absolute neutrophil count (ANC) \>= 1000/uL obtained =\< 14 days prior to registration
• Platelet count (PLT) \>= 75,000/uL obtained =\< 14 days prior to registration
• Total bilirubin =\< 2.0 mg/dL unless due to known Gilbert's disease obtained =\< 14 days prior to registration
• NOTE: If total bilirubin is \> 2 mg/dL, a direct bilirubin should be performed and must be \< 1.5 mg/dL for Gilbert's to be diagnosed
• Alanine aminotransferase (ALT/serum glutamic pyruvic transaminase \[SGPT\]) and aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x upper limit of normal (ULN) obtained =\< 14 days prior to registration
• Creatinine clearance \>= 30 mL/min/1.73 m\^2 (as determined by Cockcroft-Gault equation) obtained =\< 14 days prior to registration
• Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only

You may not qualify if:

• Recent prior chemotherapy:
• Newly diagnosed patients (regardless of group); any prior chemotherapy for POEMS with the following exceptions:
• Previously treated patients (group 2)
• Alkylators (e.g. melphalan, cyclophosphamide) =\< 28 days prior to registration
• Anthracyclines =\< 28 days prior to registration
• High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide), or proteosome inhibitors (e.g. ixazomib or bortezomib) =\< 28 days prior to registration
• Requirement for concomitant high dose corticosteroids
• EXCEPTION: Patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for adrenal insufficiency, rheumatoid arthritis, etc
• Receiving any other investigational agent, which would be considered as a treatment for the primary neoplasm
• Participation in other clinical trials, including those with other investigational agents not included in this trial, =\< 30 days prior to registration and throughout the duration of this trial
• Prior refractoriness to proteasome inhibitor or immunomodulatory drugs (IMiD)
• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Plasmacytoma; POEMS Syndrome

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ixazomib; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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

Study Officials

• Angela Dispenzieri, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: October 3, 2016
• Study Start: October 31, 2016
• Primary Completion: April 21, 2022
• Study Completion: May 13, 2024
• Last Updated: February 12, 2025

Record last verified: 2025-02

Locations

US (1)