Ibrutinib, Lenalidomide, and Dexamethasone in Treating Patients With Multiple Myeloma Ineligible for Transplant

NCT03015792 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: MC148ANCI-2017-00006
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose and side effects of ibrutinib when given together with lenalidomide and dexamethasone and how well they work in treating patients with multiple myeloma that are not eligible for transplant. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib, lenalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 (Phase I)

  Up to 28 days

• Rate of confirmed response defined as patient who has achieved a stringent (s) complete response (CR), CR, very good partial response (VGPR), or partial response (PR) on two consecutive evaluations at any time during treatment (Phase II)

  Response will be evaluated using all cycles of treatment. Responses will be summarized by simple descriptive summary statistics delineating depth of response as well as stable and progressive disease in this patient population. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 3 years

Secondary Outcomes (4)

• Progression-free survival (Phase II)

  From registration to the time of progression or death due to any cause, assessed up to 3 years

• Overall survival (Phase II)

  From registration to death due to any cause, assessed up to 3 years

• Duration of response (Phase II)

  The date at which the patient's objective status is first noted to be a sCR, CR, VGPR, or PR to the earliest date progression is documented, assessed up to 3 years

• Incidence of adverse events assessed by CTCAE v 4.0 (Phase II)

  Up to 30 days after last dose of study treatment

Other Outcomes (4)

• Compliance to treatment (Phase II)

  Up to 3 years

• QoL measured by the MD Anderson Symptom Inventory - Multiple Myeloma (Phase II)

  Up to 3 years

• BTK signalosome members (Phase II)

  Up to 3 years

Study Arms (1)

Treatment (ibrutinib, lenalidomide, dexamethasone)

EXPERIMENTAL

PHASE I: Patients receive ibrutinib PO on days 1-28, lenalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Beginning course 25, patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 84 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive ibrutinib and dexamethasone as in phase I and lenalidomide PO on days 1-21 beginning course 2. Beginning course 25, patients receive lenalidomide and dexamethasone as in phase I.

Drug: Dexamethasone; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Other: Pharmacological Study; Other: Quality-of-Life Assessment

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

Treatment (ibrutinib, lenalidomide, dexamethasone)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib, lenalidomide, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib, lenalidomide, dexamethasone)

Lenalidomide DRUG

Given PO

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

Treatment (ibrutinib, lenalidomide, dexamethasone)

Pharmacological Study OTHER

Correlative studies

Treatment (ibrutinib, lenalidomide, dexamethasone)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ibrutinib, lenalidomide, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Diagnosis
• Phase I: confirmed diagnosis of relapsed or refractory multiple myeloma
• Phase II: confirmed diagnosis of active multiple myeloma and must be newly diagnosed
• NOTE: all tests for establishing disease status must be completed =\< 28 days prior to registration
• Measurable disease =\< 28 days prior to registration, defined by at least one of the following:
• Serum monoclonal protein \>= 1.0 g/dL
• \> 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum immunoglobulin free light chain \> 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Monoclonal bone marrow plasmacytosis \> 30% (evaluable disease)
• Prior treatment
• Phase I: exposure to 2-3 prior lines of therapy or no therapeutic options
• Phase II: previously untreated for symptomatic MM
• EXCEPTION: =\< 7 days with pulse steroids or localized radiation therapy, without curative intent, for a myeloma-related complication prior to registration is allowed, as considered necessary by the treating physician
• Myeloma Frailty Score:

You may not qualify if:

• Non-secretory MM or known amyloid light-chain (AL) amyloidosis
• Clinically significant active infection requiring intravenous antibiotics =\< 14 days prior to registration
• \>= grade 3 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Other prior malignancy; EXCEPTIONS:
• Adequately treated basal cell or squamous cell skin cancer
• Any in situ cancer
• Adequately treated stage I or II cancer from which the patient is currently in complete remission, or
• Any other cancer from which the patient has been disease-free for \>= at least three years prior to registration
• Concurrent therapy considered to be investigational; NOTE: patients must not be planning to receive any radiation therapy (except localized radiation for palliative care that must be completed prior to starting cycle 1, day 1)
• Any of the following:
• Pregnant women
• Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Requires treatment with a strong cytochrome (CYP) 3A4/5 inhibitor
• Major surgery =\< 4 weeks prior to registration

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ibrutinib; 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

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

• Sikander Ailawadhi, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 10, 2017
• Study Start: March 10, 2017
• Primary Completion: October 18, 2022
• Study Completion: October 18, 2022
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

US (1)