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Recurrent Plasma Cell MyelomaPhase 1NCT03015792

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

A Phase 1 study testing Dexamethasone, Ibrutinib and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dexamethasone, Ibrutinib and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
10 Mar 2017to 18 Oct 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

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

CORRELATIVE RESEARCH OBJECTIVES:

  1. 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.

Being tested
Dexamethasone, Ibrutinib, Laboratory Biomarker Analysis, Lenalidomide, Pharmacological Study
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • Pharmacological StudyOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT03015792
Study groupRoleWhat they receive
Treatment (ibrutinib, lenalidomide, dexamethasone)ExperimentalPHASE 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.
Receives: Drug: Dexamethasone; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Other: Pharmacological Study; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Up to 28 days

  2. 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.

    Measured: Up to 3 years

Secondary outcomes (4)

  1. Progression-free survival (Phase II)

    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

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

  2. Overall survival (Phase II)

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

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

  3. Duration of response (Phase II)

    The distribution of duration of response will be estimated using the method of Kaplan-Meier.

    Measured: 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

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

    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.

    Measured: Up to 30 days after last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2017 (estimated)
  2. Study start10 Mar 2017
  3. Primary completion18 Oct 2022
  4. Study completion18 Oct 2022

Why it stopped: Drug company decided to not fund the phase 2 portion

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03015792
Sponsor's protocol ID
MC148A
Other IDs
NCI-2017-00006
Status last verified
Aug 2025
First submitted
4 Jan 2017
Last updated
17 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dexamethasone, Ibrutinib and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Drug company decided to not fund the phase 2 portion). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03015792.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.

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