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NCT02902965

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

Completed Phase 2 Results posted Last updated 16 March 2020
What this trial tests

Phase 2 trial testing Ibrutinib in Multiple Myeloma in 74 participants. Completed in 26 October 2018.

Timeline
20 September 2016
Primary endpoint
26 October 2018
26 October 2018

Quick facts

Lead sponsorPharmacyclics Switzerland GmbH
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment74
Start date20 September 2016
Primary completion26 October 2018
Estimated completion26 October 2018
Sites33 locations across Italy, Greece, Germany, Turkey (Türkiye), Spain, Czechia

Drugs / interventions tested

Conditions studied

Sponsor

Pharmacyclics Switzerland GmbH

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Median Progression-Free Survival (PFS) Primary · 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.

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone8.56.2 – 10.8
Overall Response Rate (ORR) Secondary · 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

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone56.844.7 – 68.2
Progression Free Survival (PFS) at Landmark Points - 20 Months Secondary · 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.

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone6.61.6 – 16.9
Duration of Response (DOR) Secondary · 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.

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone9.56.9 – 10.6
Overall Survival (OS) at 24 Months Secondary · 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.

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone53.638.0 – 67.0
Time to Progression (TTP) Secondary · 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.

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone10.67.8 – 12
Safety and Tolerability of Ibrutinib in Combination With Bortezomib and Dexamethasone as Measured by the Number of Participants With Adverse Events. Secondary · 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

GroupValue95% CI
Ibrutinib+ Bortezomib+ Dexamethasone74

Adverse events — posted to ClinicalTrials.gov

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).. Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ibrutinib+ Bortezomib+ Dexamethasone
Serious: 47/74 (64%)
Deaths: 27/74

Serious adverse events (66 terms)

ReactionSystemIbrutinib+ Bortezomib+ Dex…
PneumoniaInfections and infestations
Atrial fibrillationCardiac disorders
SepsisInfections and infestations
Spontaneous haematomaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Renal failureRenal and urinary disorders
HyponatraemiaMetabolism and nutrition disorders
BronchitisInfections and infestations
Lung infectionInfections and infestations
Pneumonia bacterialInfections and infestations
Pneumonia haemophilusInfections and infestations
Pneumonia pneumococcalInfections and infestations
Upper respiratory tract infectionInfections and infestations
Circulatory collapseVascular disorders
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AstheniaGeneral disorders
DeathGeneral disorders
PyrexiaGeneral disorders
Sudden deathGeneral disorders
DeliriumPsychiatric disorders
Humerus fractureInjury, poisoning and procedural complications
Spinal compression fractureInjury, poisoning and procedural complications
Thoracic vertebral fractureInjury, poisoning and procedural complications
Weight decreasedInvestigations
Atrial flutterCardiac disorders
Other adverse events (75 terms — click to expand)

ReactionSystemIbrutinib+ Bortezomib+ Dex…
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
AstheniaGeneral disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
Upper respiratory tract infectionInfections and infestations
Periperal sensory neuropathyNervous system disorders
NauseaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
LymphopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
HypocalcaemiaMetabolism and nutrition disorders
HypertensionVascular disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ConjunctivitisInfections and infestations
NasopharyngitisInfections and infestations
BronchitisInfections and infestations
HypotensionVascular disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Urinary tract infectionInfections and infestations
EpistaxisRespiratory, thoracic and mediastinal disorders
Respiratory tract infectionInfections and infestations
InsomniaPsychiatric disorders
Atrial fibrillationCardiac disorders
HeadacheNervous system disorders
Abdominal pain upperGastrointestinal disorders
Hepatic function abnormalHepatobiliary disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Peripheral swellingGeneral disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Peripheral sensorimotor neuropathyNervous system disorders
PolyneuropathyNervous system disorders

Most-reported serious reactions: Pneumonia, Atrial fibrillation, Sepsis, Spontaneous haematoma, Thrombocytopenia, Renal failure, Hyponatraemia, Bronchitis.

Data from ClinicalTrials.gov NCT02902965 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Macrophages in immunoregulation and therapeutics.
    Chen S, Saeed AFUH, Liu Q, Jiang Q, et al · · 2023 · cited 1250× · PMID 37211559 · DOI 10.1038/s41392-023-01452-1
  2. Targeting macrophages in cancer immunotherapy.
    Duan Z, Luo Y. · · 2021 · cited 462× · PMID 33767177 · DOI 10.1038/s41392-021-00506-6
  3. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway.
    Tremblay-LeMay R, Rastgoo N, Chang H. · · 2018 · cited 53× · PMID 29580288 · DOI 10.1186/s13045-018-0589-1
  4. Osteoclast Immunosuppressive Effects in Multiple Myeloma: Role of Programmed Cell Death Ligand 1.
    Tai YT, Cho SF, Anderson KC. · · 2018 · cited 47× · PMID 30147691 · DOI 10.3389/fimmu.2018.01822
  5. The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.
    Paradzik T, Bandini C, Mereu E, Labrador M, et al · · 2021 · cited 28× · PMID 33799793 · DOI 10.3390/cancers13061235
  6. Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.
    Richardson PG, Bensinger WI, Huff CA, Costello CL, et al · · 2018 · cited 27× · PMID 29435979 · DOI 10.1111/bjh.15058
  7. Bruton's Tyrosine Kinase Targeting in Multiple Myeloma.
    Von Suskil M, Sultana KN, Elbezanti WO, Al-Odat OS, et al · · 2021 · cited 15× · PMID 34071917 · DOI 10.3390/ijms22115707
  8. Recent Advances in the Applications of Small Molecules in the Treatment of Multiple Myeloma.
    Abramson HN. · · 2023 · cited 12× · PMID 36768967 · DOI 10.3390/ijms24032645

Verify or expand the search:

Other trials of Ibrutinib

Trials testing the same drug.

Other recruiting trials for Multiple Myeloma

Currently open trials in the same condition.

Other Pharmacyclics Switzerland GmbH trials

Trials by the same sponsor.

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