Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Zanubrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Zanubrutinib (160 milligrams) administered orally twice daily

Administered as specified in the treatment arm.

Study Director

The primary objective of this study was to evaluate the efficacy of zanubrutinib in participants with centrally confirmed relapsed or refractory MCL.

Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate Efficacy and Safety of BGB-3111, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR.

Progression-free survival was defined as the time from the starting date of zanubrutinib to the date of first documentation of disease progression or death, whichever occurred first. Participants who did not have disease progression were censored at their last valid tumor assessment. A six-month progression-free survival rate was defined as no disease progression after treated with zanubrutinib for over six months (under control). The 95% confidence interval (CI) lower bound was 33.1 months while the upper bound could not be estimated.

Time to response was defined as the time from treatment initiation to the first documentation of response.

The duration of response was defined as the time from the date that the response criteria are first met to the date that Progressive Disease was objectively documented or death (whichever occurs first). Participants who did not have disease progression were censored at their last valid assessment.

The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a BOR of CR or PR. The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. For this outcome measure, only investigator-assessed data are analyzed and reported because of the high rate of concordance between the Independent Review Committee and investigator assessments for the primary outcome measure of ORR.

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up visit) or initiation of new anticancer therapy, whichever comes first.

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to the study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

BeiGene

Zanubrutinib (160 mg) administered BID for over 3 years.

Zanubrutinib (160 mg) administered BID until Zanubrutinib (160 milligrams \[mg\]) administered orally twice daily (BID) until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.

Age, Continuous

< 65 years

≥ 65 years

Age, Customized

Sex: Female, Male

Chinese

Race/Ethnicity, Customized

China

Region of Enrollment

Participants' MCL disease stage at consent date, with higher stages indicating more severe MCL.

Mantle Cell Lymphoma (MCL) Disease Stage at Study Entry

Disease Status

Grade 0 = Fully active, able to carry on all pre-disease performance without restriction; Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work; Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; Lower grades indicate better outcome.

Eastern Cooperative Oncology Group Performance Status

Safety Analysis Set: All participants who received any dose of study drug.

A binomial exact test was performed to test against the null hypothesis H0: ORR=0.40 using the significant level of 0.025 (1-sided)

Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.

Overall Response Rate (ORR) As Assessed By Independent Review Committee

Progression-free Survival

Time To Response

Duration Of Response

ORR As Assessed By The Investigator

Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)

Number Of Participants Experiencing AEs Leading To Treatment Discontinuation

Zanubrutinib (160 milligrams \[mg\]) administered orally twice daily (BID) until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.

Overall Study

Anti-Infective Agents

Sirolimus

Ibrutinib

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

560 mg once daily continuous (without interruption) by mouth for 21-day cycles

175 mg once daily intravenous infusion on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each 21-day cycle

Janssen Research & Development, LLC Clinical Trial

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.

This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known), study to evaluate the efficacy and safety of ibrutinib when compared with temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 1 prior rituximab-containing chemotherapy regimen. Approximately 280 eligible patients will be randomly assigned in a 1:1 ratio and stratified (grouped) by the number of prior lines of therapy (1 or 2 versus \>=3) and simplified MCL International Prognostic Index criteria to receive either ibrutinib by mouth (Treatment Arm A) or temsirolimus intravenous infusion (Treatment Arm B). The study will consist of screening, treatment, and posttreatment phases. Data will be collected on disease response to the treatment, progression-free survival, overall survival, subsequent anti-MCL therapies, patient reported outcomes, and medical resource utilization. Tumor samples, blood collected at multiple time points, and a bone marrow aspirate will be evaluated to identify markers predictive of response or resistance to ibrutinib. Serial pharmacokinetic (study of what the body does to a drug) samples will be collected as detailed in the protocol. Safety will be monitored throughout the study. Disease evaluations will be performed every 9 weeks for up to 15 months from the start of study drug, and every 24 weeks thereafter, until disease progression, death, or the clinical cutoff, whichever comes first. Patients who receive treatment with temsirolimus and have disease progression (confirmed by an Independent Review Committee) may be eligible to crossover and receive treatment with ibrutinib 560 mg orally, daily, on a 21-day cycle until disease progression, unacceptable toxicity, or study end. Data will be analyzed up to 3 years after the last patient is enrolled for the final follow-up.

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

A Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

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

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.

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

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

Biomarker evaluations to identify markers altering BCR signaling or activate alternative signaling pathways and explore their association with response or resistance to ibrutinib. Next-generation sequencing at baseline identifies possible primary resistance mutations and those found only at progression are acquired mutations on therapy.

Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.

The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and possible total score range -0.594 to 1; higher score indicates a better health state.

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).

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.

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

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.

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

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.

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.

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.

Pharmacyclics LLC.

Janssen Research & Development, LLC

Safety population included all randomized participants who received at least 1 dose of study agent (ibrutinib or temsirolimus) during the treatment phase.

Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.

Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.

Total

Age, Categorical

Female

Male

Sex/Gender, Customized

Belgium

Brazil

Canada

Colombia

Czech Republic

Germany

Spain

France

United Kingdom

Hungary

Ireland

Italy

South Korea

Mexico

Netherlands

Poland

Portugal

Russian Federation

Sweden

Taiwan

Ukraine

Director, Clinical Research

The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Progression Free Survival (PFS)

Overall Response Rate (ORR)

Overall Survival (OS)

The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants responded for this outcome measure.

Duration of Response

Time-to-Next Treatment

Progression-Free Survival 2

Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)

Safety population included all randomized participants who received at least 1 dose of the study drug.

Number of Participants Affected With Treatment-emergent Adverse Events

Time to Response

Safety Analyses Set (SAS) population includes all the randomized participants who received at least 1 dose of study agent (ibrutinib or temsirolimus) during the treatment phase.

Extent of Exposure of Time

One Year Survival Rate

Pharmacokinetic analysis set included the participants who had received one dose of study drug had at least 1 pharmacokinetic sample obtained post-treatment.

Area Under the Plasma Concentration of Ibrutinib During Steady State (AUC-ss)

Number of Participants With Biomarkers That Alter B-cell Receptor (BCR) Signaling or Activate Alternative Signaling Pathways and to Explore Their Association With Response or Resistance to Ibrutinib

Number of Hospitalizations Reported Related Medical Resource Utilization Information (MRUI)

Number of Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)

Mean days of hospitalization

Mean days of emergency room visits

Days of Hospitalization and Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)

Baseline

Change at Cycle 2

Change at Cycle 3

Change at Cycle 4

Change at Cycle 5

Change at Cycle 6

Change at Cycle 7

Change at Cycle 8

Change at Cycle 11

Change at Cycle 14

Change at Cycle 17

Change at Cycle 20

Change at Cycle 28

Change at Cycle 36

Change at End of treatment

The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants evaluated for this outcome measure.

The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment

Analgesics

Antirheumatic Agents

Mitoxantrone

Fludarabine

Fludarabine phosphate

Rituximab

Antineoplastic Agents, Immunological

Drug: Fludarabine Given on days 1-3 of each 28-day cycle Drug: Mitoxantrone Given on day 1 of each 28-day cycle Drug: Rituximab Given on day 1 of each 28-day cycle Drug: Zevalin Given after two cycles if there is no disease progression.

After two cycles if there is no disease progression, zevalin treatment will be given. Rituximab will be given followed by an imaging dose of zevalin. Two or three scans will be performed over a week to determine if it is safe to give the full treatment dose of zevalin. The treatment dose is given with the second infusion or rituximab, seven days after the first dose.

Zevalin

Jennifer R Brown, MD, PhD

* The purpose of this study is to find out whether combining a short course of chemotherapy (Fludarabine, Mitoxantrone and Rituximab) followed by Zevalin will be effective in treating relapsed mantle cell lymphoma.
* The secondary purposes of the study are to determine the safety and to evaluate whether there is additional benefit from Zevalin therapy following the chemotherapy.

* Patients receive fludarabine (days 1-3), mitoxantrone (day 1), and rituximab (day 1) of each 28-day cycle.
* Patients undergo a CT scan and bone marrow biopsy after two cycles. Unless the cancer has progressed, the patient will then receive Zevalin study treatment.
* Blood counts are taken every week for 12 weeks. After 12 weeks, a CT scan and bone marrow biopsy are performed.
* Long-term followup is 4 years. Physical exam and blood work is performed every 3 months for the first two years. Following that, physical exams and blood work is every 6 months for another two years. CT scans and bone marrow biopsies are every 6 months during this 4 year followup period.

Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

Abbreviated Fludarabine / Mitoxantrone / Rituximab Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

Massachusetts General Hospital

Biogen

Dana-Farber Cancer Institute

Assistant Professor of Medicine

Gemcitabine

Cytarabine

Lenalidomide

Chlorambucil

Antimetabolites

Angiogenesis Inhibitors

Growth Inhibitors

Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, Fludarabine

For patients with a creatinine clearance of ≥ 60 mL/min: 25 mg daily x 21 days of a 28 day cycle until disease progression or unacceptable toxicity.

For patients who have a moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min: 10 mg daily x 21 days of a 28 day cycle (Cycles 1 and 2). After Cycle 2, if the patient remains free of Grade 3 or Grade 4 toxicity, the dose will be increased to 15 mg daily x 21 days of a 28 day cycle until disease progression or unacceptable toxicity.

Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, or Fludarabine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)	NCT03206970	Refractory Mant... Relapsed Mantle...	Zanubrutinib	18 Years - 75 Years	BeiGene
Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)	NCT03206970	Refractory Mant... Relapsed Mantle...	Zanubrutinib	18 Years - 75 Years	BeiGene
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	NCT01646021	Mantle Cell Lym...	Ibrutinib Temsirolimus	18 Years -	Janssen Research & Development, LLC
Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma	NCT00119730	Mantle Cell Lym...	Fludarabine Mitoxantrone Rituximab Zevalin	18 Years -	Dana-Farber Cancer Institute
Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma	NCT00119730	Mantle Cell Lym...	Fludarabine Mitoxantrone Rituximab Zevalin	18 Years -	Dana-Farber Cancer Institute
A Study to Determine the Efficacy of Lenalidomide Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)	NCT00875667	Mantle Cell Lym... Lymphoma, Mantl...	Lenalidomide Investigators c...	18 Years -	Celgene
A Study to Determine the Efficacy of Lenalidomide Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)	NCT00875667	Mantle Cell Lym... Lymphoma, Mantl...	Lenalidomide Investigators c...	18 Years -	Celgene

Spots Global Cancer Trial Database for relapsed mantle cell lymphoma