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NCT01646021

Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

Completed Phase 3 Results posted Last updated 19 January 2018
What this trial tests

Phase 3 trial testing Ibrutinib in Mantle Cell Lymphoma in 280 participants. Completed in 15 December 2016.

Timeline
10 December 2012
Primary endpoint
5 June 2015
15 December 2016

Quick facts

Lead sponsorJanssen Research & Development, LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment280
Start date10 December 2012
Primary completion5 June 2015
Estimated completion15 December 2016
Sites92 locations across Colombia, Taiwan, Ireland, Poland, South Korea, Netherlands, Russia, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

18 and older, any sex, with Mantle Cell Lymphoma. 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.

Progression Free Survival (PFS) Primary · Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)

PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to \[\>=\] 50 percent \[%\] of previously involved sites from nadir).

GroupValue95% CI
Ibrutinib15.610.6 – 25.1
Temsirolimus6.24.2 – 7.8
Overall Response Rate (ORR) Secondary · Approximately up to 48 months

ORR is defined as the percentage of participants who achieved either CR or PR as best overall response based on the investigator assessment. CR is Disappearance of all target lesions while PR is greater than or equal to 30 % decrease in the sum of the longest diameter of target lesions and Overall Response (OR) is sum of CR and PR.

GroupValue95% CI
Ibrutinib77.0
Temsirolimus46.8
Overall Survival (OS) Secondary · Approximately up to 48 months

Overall survival (OS) was defined as the interval between the date of randomization and the date of death from any cause.

GroupValue95% CI
Ibrutinib30.319.1 – 42.1
Temsirolimus23.513.0 – 30.7
Duration of Response Secondary · Approximately up to 48 months

Duration of response (CR or PR), defined as the duration in days from the date of initial response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. The analysis was based on the investigator assessment.

GroupValue95% CI
Ibrutinib23.116.2 – 28.1
Temsirolimus6.34.7 – 8.6
Time-to-Next Treatment Secondary · Approximately up to 48 months

Time to next treatment was measured from the date of randomization to the start date of any anti-neoplastic treatment subsequent to study treatment.

GroupValue95% CI
Ibrutinib31.823.3 – NA
Temsirolimus11.68.0 – 13.3
Progression-Free Survival 2 Secondary · Approximately up to 48 months

Progression-free survival 2 defined as the time interval between the date of randomization and date of event, defined as progressive disease as assessed by investigator that started after the next line of subsequent anti-neoplastic therapy (including cross-over to ibrutinib), death from any cause, or the start of the second subsequent anti-neoplastic therapy if no progressive disease was recorded after the first subsequent anti-neoplastic therapy.

GroupValue95% CI
Ibrutinib26.217.2 – 32.4
Temsirolimus15.410.2 – 21.3
Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym) Secondary · Approximately up to 48 months

Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life.

GroupValue95% CI
IbrutinibNA81.4 – NA
Temsirolimus10.66.6 – 15.3
Number of Participants Affected With Treatment-emergent Adverse Events Secondary · Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years)

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

GroupValue95% CI
Ibrutinib139
Temsirolimus138
Time to Response Secondary · Approximately up to 2.8 years

Time to response for participants with CR/PR, defined as the interval between the date of randomization and date of initial documentation of response.

GroupValue95% CI
Ibrutinib2.150.5 – 10.4
Temsirolimus2.140.9 – 12.0
Extent of Exposure of Time Secondary · Approximately up to 46.8 months

Extent of exposure is defined as the duration of the treatment administered during the study. Duration of exposure is calculated as the number of months between the start and end of treatment.

GroupValue95% CI
Ibrutinib14.390.0 – 46.8
Temsirolimus3.020.0 – 31.4
One Year Survival Rate Secondary · Month 12

One -year survival rate, defined as the proportion of participants who were alive 1 year after randomization.

GroupValue95% CI
Ibrutinib0.680.59 – 0.75
Temsirolimus0.610.52 – 0.69
Area Under the Plasma Concentration of Ibrutinib During Steady State (AUC-ss) Secondary · Cycle 1 and 2 (Day 1): Predose, 1, 2, 4 hr. postdose; Cycle 3 (day 1): Predose (Each cycle is of 21 days)

The AUC-ss is the area under the plasma concentration time curve observed during steady state.

GroupValue95% CI
Ibrutinib561.6± 448

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately up to 4 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ibrutinib
Serious: 79/139 (57%)
Deaths: 130/139
Temsirolimus
Serious: 83/139 (60%)
Deaths: 137/139

Serious adverse events (180 terms)

ReactionSystemIbrutinibTemsirolimus
PneumoniaInfections and infestations
Atrial FibrillationCardiac disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pleural EffusionRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal PainGastrointestinal disorders
General Physical Health DeteriorationGeneral disorders
DiarrhoeaGastrointestinal disorders
Multi-Organ FailureGeneral disorders
Renal FailureRenal and urinary disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
Urinary Tract InfectionInfections and infestations
Tumour Lysis SyndromeMetabolism and nutrition disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Febrile NeutropeniaBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
Device Related InfectionInfections and infestations
GastroenteritisInfections and infestations
InfectionInfections and infestations
Lower Respiratory Tract InfectionInfections and infestations
Lung InfectionInfections and infestations
Other adverse events (72 terms — click to expand)

ReactionSystemIbrutinibTemsirolimus
ThrombocytopeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NeutropeniaBlood and lymphatic system disorders
Oedema PeripheralGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
StomatitisGastrointestinal disorders
Upper Respiratory Tract InfectionInfections and infestations
AstheniaGeneral disorders
PyrexiaGeneral disorders
Decreased AppetiteMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Muscle SpasmsMusculoskeletal and connective tissue disorders
HypertriglyceridaemiaMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
HypokalaemiaMetabolism and nutrition disorders
Platelet Count DecreasedInvestigations
ConstipationGastrointestinal disorders
Mucosal InflammationGeneral disorders
Blood Creatinine IncreasedInvestigations
Weight DecreasedInvestigations
HypercholesterolaemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
ConjunctivitisInfections and infestations
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
HypertensionVascular disorders
Oral HerpesInfections and infestations
Back PainMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
PneumoniaInfections and infestations
Respiratory Tract InfectionInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pain in ExtremityMusculoskeletal and connective tissue disorders
Abdominal PainGastrointestinal disorders
SinusitisInfections and infestations

Most-reported serious reactions: Pneumonia, Atrial Fibrillation, Pyrexia, Sepsis, Dyspnoea, Pleural Effusion, Anaemia, Thrombocytopenia.

Data from ClinicalTrials.gov NCT01646021 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus temsirolimus in patients with relapsed or refractory mantle cell lymphoma who received at least 1 prior chemotherapy regimen.

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. Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non-Germinal Center B-Cell Diffuse Large B-Cell Lymphoma.
    Younes A, Sehn LH, Johnson P, Zinzani PL, et al · · 2019 · cited 436× · PMID 30901302 · DOI 10.1200/jco.18.02403
  4. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.
    Dreyling M, Jurczak W, Jerkeman M, Silva RS, et al · · 2016 · cited 343× · PMID 26673811 · DOI 10.1016/s0140-6736(15)00667-4
  5. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  6. BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.
    Alu A, Lei H, Han X, Wei Y, et al · · 2022 · cited 88× · PMID 36183125 · DOI 10.1186/s13045-022-01353-w
  7. Advances in targeted therapy for malignant lymphoma.
    Wang L, Qin W, Huo YJ, Li X, et al · · 2020 · cited 88× · PMID 32296035 · DOI 10.1038/s41392-020-0113-2
  8. Bruton's tyrosine kinase: from X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies.
    Ponader S, Burger JA. · · 2014 · cited 86× · PMID 24778403 · DOI 10.1200/jco.2013.53.1046

Verify or expand the search:

Other trials of Ibrutinib

Trials testing the same drug.

Other recruiting trials for Mantle Cell Lymphoma

Currently open trials in the same condition.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01646021.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing