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

August 13, 2025 updated by: Mayo Clinic

Phase I/II Trial of Ibrutinib, Dexamethasone, and Lenalidomide as Initial Therapy for Transplant Ineligible Multiple Myeloma Patients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of ibrutinib that can be combined with lenalidomide and dexamethasone in relapsed multiple myeloma (MM) patients. (Phase I) II. To estimate the overall response rate (ORR) including partial response (PR) or better of the combination of ibrutinib, lenalidomide, and dexamethasone in subjects with newly diagnosed MM who are not candidates for high dose chemotherapy and autologous stem cell transplantation (ASCT). (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of this regimen in relapsed MM patients. (Phase I) II. To evaluate the progression free survival (PFS) of the combination of ibrutinib, lenalidomide, and dexamethasone in MM patients. (Phase II) III. To evaluate the safety profile of this regimen in untreated MM patients. (Phase II) IV. To evaluate the duration of response for patients treated with this 3-drug regimen. (Phase II) V. To evaluate overall survival (OS) for patients treated with this 3-drug regimen. (Phase II)

EXPLORATORY OBJECTIVES:

I. To explore compliance to treatment. II. To assess effects of treatment on patient-reported quality of life (QoL) measures.

CORRELATIVE RESEARCH OBJECTIVES:

I. To determine the role of members of the BTK signalosome in achievement or lack thereof of response to ibrutinib.

II. To explore biologic effects of ibrutinib on microenvironment in MM and correlate with response to treatment.

III. To evaluate pharmacodynamic measures including receptor occupancy for BTK prior to introducing lenalidomide in patients treated with ibrutinib and dexamethasone.

IV. To evaluate the impact of ibrutinib on platelet aggregation.

OUTLINE: This is a phase I, dose-escalation study of ibrutinib followed by a phase II study.

PHASE I: Patients receive ibrutinib orally (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.

After completion of study treatment, patients are followed up every 3 months, then every 6 months for up to 3 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    • NOTE: this will include calculating a frailty score (based on age, activities of daily living, instrumental activities of daily living and Charlson comorbidity index)

      • Phase I: "intermediate fitness" or "frail"; NOTE: no "fit" patients will be included in the phase 1 portion of the trial which is being done to determine the MTD of the 3-drug combination
      • Phase II: transplant-ineligible as per their treating physician; NOTE: all the patients with "intermediate fitness" or "frail" status will be considered transplant-ineligible; other reasons to consider transplant ineligibility may include, but are not limited to: financial constraints or patient preference; in case such patients have a frailty score of "fit", it should be duly noted by the treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support (obtained =< 14 days prior to registration)
  • Platelets >= 50,000 cells/mm^3 for patients who have bone marrow (obtained =< 14 days prior to registration)
  • Plasmacytosis < 50% or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50% (obtained =< 14 days prior to registration)
  • Calculated or measured creatinine clearance >= 30 ml/min (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's syndrome (obtained =< 14 days prior to registration)
  • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN (obtained =< 14 days prior to registration)
  • Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 X ULN (obtained =< 14 days prior to registration)
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Persons able to become pregnant must be willing to adhere to the scheduled pregnancy testing as required in the REVLIMID Risk Evaluation and Mitigation Strategy (REMS) program
  • Willing to be registered into the mandatory REVLIMID REMS program, and willing and able to comply with the requirements of the REVLIMID REMS program
  • Ability to complete study-related (QoL, pill diary) questionnaire(s) by themselves or with assistance
  • Willing to provide bone marrow aspirate and core, and blood samples for correlative research purposes

Exclusion Criteria:

  • 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
  • History of stroke/intracranial hemorrhage =< 6 months prior to registration

  • Requires use of therapeutic anticoagulation prior to registration

    • NOTE: thromboprophylaxis with any agent is permitted
  • History of clinically significant bleeding or known platelet or coagulation disorder
  • Clinically significant cardiac illness including New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias noted =< 14 days prior to registration

  • Hepatic impairment:

    • Phase I: any currently active, clinically significant hepatic impairment (Child-Pugh class A, B, or C according to the Child Pugh classification)
    • Phase II: currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification

  • Known human immunodeficiency virus (HIV) positive (+) patients; EXCEPTION: if they meet the following additional criteria =< 28 days prior to registration:

    • CD4 cells >= 500/mm^3
    • Viral load of < 50 copies HIV messenger (m) ribonucleic acid (RNA)/mm^3 if on combination antiretroviral therapy (cART) or < 10,000 copies HIV mRNA if not on cART • No zidovudine or stavudine as part of cART
  • Known hepatitis B or hepatitis C infection; EXCEPTION: if viral load < 800,000 IU/L
  • Phase I: active dermatologic disease >= grade 3

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (ibrutinib, lenalidomide, dexamethasone)

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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Pharmacological Study
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • Revlimid
  • CC5013
  • CDC 501
Drug: Dexamethasone
Given PO
Other Names:
  • Decadron
  • Hemady
  • 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 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
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Drug: Ibrutinib
Given PO
Other Names:
  • PCI-32765
  • Imbruvica
  • BTK Inhibitor PCI-32765
  • CRA-032765

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to 28 days
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)
Time Frame: Up to 3 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of response (Phase II)
Time Frame: 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
The distribution of duration of response will be estimated using the method of Kaplan-Meier.
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
Progression-free survival (Phase II)
Time Frame: From registration to the time of progression or death due to any cause, assessed up to 3 years
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
From registration to the time of progression or death due to any cause, assessed up to 3 years
Overall survival (Phase II)
Time Frame: From registration to death due to any cause, assessed up to 3 years
The distribution of survival time will be estimated using the method of Kaplan-Meier.
From registration to death due to any cause, assessed up to 3 years
Incidence of adverse events assessed by CTCAE v 4.0 (Phase II)
Time Frame: Up to 30 days after last dose of study treatment
The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Up to 30 days after last dose of study treatment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Compliance to treatment (Phase II)
Time Frame: Up to 3 years
Patient compliance to ibrutinib, dexamethasone, and lenalidomide will be assessed by means of self-reported and healthcare staff assessed pill count/diary. Correlation between medication adherence and disease response will be assessed.
Up to 3 years
QoL measured by the MD Anderson Symptom Inventory - Multiple Myeloma (Phase II)
Time Frame: Up to 3 years
Up to 3 years
BTK signalosome members (Phase II)
Time Frame: Up to 3 years
Will be profiled by MSD-based mesoscale assay (or phospho-flow) at baseline before treatment, after cycle 1 (phase II patients only), and at the time of response assessment or disease progression. BTK signalosome component expression levels will be determined from BM and/or peripheral blood. Each measure will be summarized descriptively at each time point and changes across time will be evaluated. Correlation with response to overall therapy will be assessed using Wilcoxon's rank sum tests.
Up to 3 years
T-cells populations modulation (Phase II)
Time Frame: Up to 3 years
Will conduct flow cytometry/fluorescence activated cell sorting (FACS) analysis to identify percentages of the immune cell populations (T-cells, natural killer cells, macrophages) in the bone marrow and peripheral blood at baseline before treatment, after cycle 1 (phase II patients only) and at the time of response assessment or disease progression. Each measure will be summarized descriptively at each time point and changes across time will be evaluated. Correlation with response to overall therapy will be assessed using Wilcoxon's rank sum tests.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sikander Ailawadhi, M.D., Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 10, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 18, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 18, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 6, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 10, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MC148A (Mayo Clinic in Florida)
  • NCI-2017-00006 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Refractory Plasma Cell Myeloma

Clinical Trials on Laboratory Biomarker Analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings