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NCT Number: NCT02902965

Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma

This is a Phase 2 open-label study to evaluate the efficacy and safety of ibrutinib in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma.

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Key information

Conditions

Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Fakultní nemocnice Brno, Brno, Czechia

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About this study

Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoeitic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. Ibrutinib is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of ibrutinib in combination with bortezomib and dexamethasone in subjects with relapsed/relapsed and refractory multiple myeloma.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects with multiple myeloma (MM) who have received 1-3 prior lines of therapy and have demonstrated disease progression since the completion of the most recent treatment regimen. (Subjects may have received prior bortezomib exposure if it does not meet the exclusion criteria for prior proteasome inhibitor use)
  • Measurable disease defined by at least one of the following:
  • Serum monoclonal protein (SPEP) ≥1 g/dL (for subjects with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE) or immunoglobulin M (IgM) multiple myeloma SPEP ≥0.5 g/dL)
  • Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine electrophoresis
  • Adequate hematologic, hepatic and renal function
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

Exclusion criteria

  • Subject must not have primary refractory disease
  • Refractory or non-responsive to prior proteasome inhibitor (PI) therapy (bortezomib or carfilzomib)
  • Peripheral neuropathy Grade ≥2 or Grade 1 with pain at Screening
  • Plasma cell leukemia, primary amyloidosis, or POEMS syndrome
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function
  • Requires treatment with strong CYP3A inhibitors
  • Women who are pregnant or breast feeding

Treatment and study plan

Ibrutinib

Drug

Ibrutinib 840 mg orally, once daily continuously starting day 1 of cycle 1 until confirmed disease progression, unacceptable toxicity or other protocol specified reason for discontinuation

Other names: Imbruvica

bortezomib

Drug

Cycles 1-8: (21-day cycle): Bortezomib 1.3 mg/m^2 sub-cutaneously on days 1, 4, 8, and 11 of each Cycle Cycles 9-12: (42-day cycle): Bortezomib 1.3 mg/m^2 sub-cutaneously on days 1, 8, 22 and 29 of each Cycle

Other names: Velcade

Dexamethasone

Drug

Cycles 1-8: (21-day cycle): Dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle Cycles 9-12: (42-day cycle): Dexamethasone 20 mg orally on days 1, 2, 8, 9, 22, 23, 29 and 30 of each cycle Cycles 13+ (28-day cycle): Dexamethasone 40 mg orally once weekly

Dose adjustment of dexamethasone to 10 mg on days specified during cycles 1-12 and 20 mg weekly during cycles 13+ is recommended for subjects >75 years of age.

Following implementation of Protocol Amendment 4, dexamethasone administration was reduced to Days 1, 4, 8 and 11 during each 21-day cycle (Cycles 1-8) and on Days 1, 8, 22, 29 on each 42-day cycle (Cycles 9-12) and unchanged thereafter.

Primary outcomes

  1. Median Progression-Free Survival (PFS)

    Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64). Participants were evaluated for Progression-Free Survival (PFS) during their entire time on the study.

    The primary efficacy endpoint of this study is mPFS. Progression free survival is defined as the time from the date of first dose of study treatment to confirmed disease progression or death from any cause, whichever occurs first.

Secondary outcomes

  1. Overall Response Rate (ORR)

    Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64). Participants were evaluated for Overall Response (OR) during the entire time on the study.

    Overall Response Rate is the percentage of participants who achieve a PR or better over the course of the study but prior to initiation of subsequent anti-cancer therapy

  2. Progression Free Survival (PFS) at Landmark Points - 20 Months

    Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64), with the 20 month Progression-Free Survival (PFS) rate presented based on Kaplan-Meier estimates.

    PFS at landmark points are the percentage of participants without progression (i.e., KM estimates) at the landmark time endpoints.

  3. Duration of Response (DOR)

    Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64).

    The time interval between the date of initial documentation of a response (PR or better) and the date of first documented evidence of PD, death, or date of censoring for the participants not progressed/died. The censoring date is the last adequate tumor assessment date.

  4. Overall Survival (OS) at 24 Months

    Time frame: The median time on study was 19.6 months (0.16+, 24.64), with the 24 month Overall Survival (OS) rate presented based on Kaplan-Meier estimates.

    As the median overall survival has not been reached, the data for the landmark analysis at 24 months are provided.

  5. Time to Progression (TTP)

    Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64).

    Time from date of first dose of study treatment to the date of first documented evidence of PD or date of censoring for the participants not progressed. The censoring date is the last adequate tumor assessment date.

  6. Safety and Tolerability of Ibrutinib in Combination With Bortezomib and Dexamethasone as Measured by the Number of Participants With Adverse Events.

    Time frame: From first dose of Ibrutinib to within 30 days of last dose for each participant or until study closure. This is the median treatment duration for Ibrutinib of 5.7 months (range: 0.1 - 23.7 months) +30 days (Adverse Events collection period).

    Safety and tolerability of ibrutinib in combination with bortezomib and dexamethasone as measured by the frequency and type of adverse events graded using the NCI CTCAE v 4.03. Frequency and Type of Adverse Events are reported in the Adverse Events module

Sponsors and collaborators

Lead sponsor

Pharmacyclics Switzerland GmbH

Industry

Collaborators

  • Janssen Research & Development, LLC

Registry information

Official study title

An Open-label Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Sep 16, 2016
Registry last updated
Mar 16, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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