Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Atezolizumab

Immunomodulating Agents

Durvalumab

Ibrutinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).

Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.

Isaiah Dimery

This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.

A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors

A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors

Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.

AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1

Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.

Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1

BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.

Pharmacyclics LLC.

Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.

All subjects who received at least one dose of study treatment.

Phase 1b/2

All participants who received at least one dose of study treatment.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline analysis population includes all patients that received at least one dose of study treatment.

Thorsten Graef

In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).

Phase 1b

Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.

Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.

Phase 2

The Response-evaluable population was participants who received at least 1 dose of treatment (ibrutinib and durvalumab) and provided 1 post-baseline response assessment.

Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data.

Phase 1b/2 (Pharmacokinetic Population)

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b and Phase 2 because the dose was the same.

Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b/2 because the dose was the same.

Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib

Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)

Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)

Phase 1b: Pharmacodynamics

Participants who enrolled and received at least 1 dose of study treatment.

Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)

All subjects who received at least one dose of ibrutinib and who had at least one evaluable BTK occupancy assay result at Cycle 3 Day 1.

Phase 2: Pharmacodynamics

Period 1

Period 2

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Bortezomib

Participants were enrolled and received 560 mg/day dose, stratified into 2 groups based on prior bortezomib exposure.

PCI-32765

Darrin Beaupre, MD, PhD

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

The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.

This is a Phase 2, open-label, nonrandomized, multicenter, monotherapy study in subjects with histologically documented MCL who have relapsed after ≥ 1 (but not \> 5) prior treatment regimens. All subjects meeting eligibility criteria will receive PCI-32765 capsules at a dosage of 560 mg/day once daily for a 28-day cycle until disease progression, unacceptable toxicity, or enrollment in a long-term extension study, whichever occurs earlier.

Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)

Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma

The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator. CR is a complete disappearance of all disease, no new lesions, lymph nodes must have regressed and be PET negative, spleen and liver should not be palpable and without nodules, and bone marrow must be negative. PR is a \>/= 50% decrease in the sum of the product of diameters of the target lesions, and \>/= 50% decrease of splenic and hepatic nodules from baseline, no new lesions and no increase in the size of liver, spleen or non-target lesions.

Number of participants who had experienced at least one treatment emergent AE

Area under the plasma concentration-time curve using data collected at 0, 1, 2, 4, 6-8, and 24 hours post dose (AUC0-24h)

Mean change from baseline to Cycle 5 in the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) Global Health Status Score according to EORTC QLQ-C30 Scoring Manual (3rd Edition, 2001). For global health status, positive changes indicated better health status or functioning, and negative changes indicated worsening of health status or functioning. Scale scores range from 0 to 100. A change in 5 to 10 points in either direction represents a small change; 10 to 20 points represents a moderate change and greater than 20 points represents a large change.

Janssen Pharmaceuticals

Poland

Germany

United Kingdom

One hundred fifteen subjects were enrolled and 111 subjects received at least 1 dose of ibrutinib and constitute the all treated population and the safety analysis set.

Dr. Darrin Beaupre

Participants who received at least 1 dose of PCI-32765 and constitute the all treated population

Percentage of Participants Achieving Response

Number of Participants With Treatment Emergent Adverse Events (AEs)

PCI-32765 - Day 8

PCI-45227 (Metabolite)- Day 8

PK samples were collected in a subset of participants (n=48) in this trial (n=111). PK parameters reported here reflects those that were PK evaluable from the 48 participants.

PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765

Participants received PCI-32765 560 mg daily and completed the EORTC QLQ-C30 questionnaire at Pre-Dose and at Cycle 5

EORTC QLQ-C30

Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score

Overall Study

Venetoclax

Subjects are enrolled into the open-label Safety Run-in Period to evaluate the occurrence of tumor lysis syndrome (TLS) and DLTs with the concurrent administration of ibrutinib and venetoclax.

Safety run-in phase for the study is closed to further enrollment as of 07-Nov-2018.

Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

This open-label arm is designed to explore the efficacy and safety of the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL.

Approximately 75 subjects (of which \~25 subjects with TP53 mutation) will be enrolled and treated with ibrutinib and venetoclax.

Placebo Oral tablet to match Venetoclax

This Phase 3 multinational, randomized, double-blind study is designed to compare the efficacy and safety of the combination of ibrutinib and venetoclax vs. ibrutinib and placebo in subjects with MCL.

Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)

Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma

To evaluate the occurrence of tumor lysis syndrome (TLS) with the concurrent administration of ibrutinib and venetoclax.

To evaluate the occurrence of DLTs with the concurrent administration of ibrutinib and venetoclax.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

ORR is defined as CR or PR per investigator assessment according to the Revised Response Criteria for Malignant Lymphoma.

DOR is defined as participants who achieve an overall response as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurs first.

To evaluate PFS of ibrutinib and venetoclax compared to ibrutinib and placebo.

OS is defined as the time from the date of the first dose of study treatment to death from any cause.

To evaluate the complete response (CR) rate with the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL

Complete response rate (CR) based on the best overall response per investigator assessment according to the Revised Response Criteria for Malignant Lymphoma.

MRD-negative remission is defined as undetectable MRD at documented CR in subjects who were MRD positive at screening as assessed by flow cytometry in bone marrow and/or peripheral blood, with requirement of confirmation of MRD negativity in the subsequent peripheral blood 12 weeks later.

TTNT is defined as the duration from the date of randomization to the start date of any anti-lymphoma treatment subsequent to study treatment.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Time to worsening in FACT-Lym subscale of the health-related quality of life questionnaire (FACT-Lym) will be compared between treatment arms.

Duration of CR, defined for subjects who achieve CR as the time from the first occurrence of CR to disease progression or death, whichever occurs first.

Janssen Research & Development, LLC

Heart and Blood Diseases

Waldenstrom Macroglobulinemia

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Antirheumatic Agents

Rituximab

Immunologic Factors

Ibrutinib: 420 mg (3 capsules x 140 mg) orally administered daily beginning from Day 1. Rituximab: 375 mg/m\^2 intravenous (IV) per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1. Rituximab: 375 mg/m\^2 IV per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1.

Participants will receive 420 mg of Ibrutinib orally.

Participants will receive placebo capsules orally.

Placebo

Participants will receive rituximab 375 mg/m\^2 IV.

Bernhard Hauns, MD

The purpose of this study is to evaluate the safety and efficacy of ibrutinib in combination with rituximab in participants with Waldenström's macroglobulinemia (WM).

Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia

iNNOVATE Study: A Randomized, Double-Blind, Placebo- Controlled, Phase 3 Study of Ibrutinib or Placebo in Combination With Rituximab in Subjects With Waldenström's Macroglobulinemia

Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.

PFS was defined as the time from date randomization to date of first IRC-confirmed disease progression (PD) assessed according to the modified VIth International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria (National Comprehensive Cancer Network \[NCCN\] 2014) or death due to any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death.

As the median PFS was not reached in the Ibrutinib + Rituximab arm at the time of the analysis, Kaplan Meier landmark estimate of the PFS rate at 54 months (that is, the estimated percentage of participants with PFS at Month 54) is presented.

ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), very good partial response (VGPR), or partial response (PR) per the IRC assessment at or prior to initiation of subsequent antineoplastic therapy and confirmed by 2 consecutive assessments. IRC assessment of response was conducted according to the modified VIth IWWM (NCCN 2014) criteria and incorporated assessments from the central radiology review. CR required complete resolution of lymphadenopathy/splenomegaly if present at baseline. VGPR and PR required reduction in lymphadenopathy/splenomegaly if present at baseline.. Kaplan-Meier estimate.

TTnT was measured from the date of randomization to the start date of any subsequent WM treatment. Participants without subsequent treatment were censored at the date of the last study visit.

As the median TTnT was not reached in the Ibrutinib + Rituximab arm and the Open-Label Substudy arm at the time of the analysis, Kaplan Meier landmark estimate of the TTnT rate at 54 months (that is, the estimated percentage of participants not receiving subsequent WM treatment at Month 54) are presented.

Percentage of participants achieving a sustained improvement in Hgb at or prior to initiation of subsequent antineoplastic therapy. Hgb improvement is defined as an increase of ≥ 2 g/dL over baseline regardless of baseline value, or an increase to \>11 g/dL with a ≥0.5 g/dL improvement if baseline is ≤ 11 g/dL. Sustained Hgb improvement is defined as improvement that is sustained continuously for ≥ 56 days (8 weeks) without blood transfusion or growth factors, which includes hemoglobin \> 110 g/L with at least a 5 g/L improvement if baseline ≤110 g/L or increase ≥20 g/L over baseline.

Percentage of participants with ≥ 3 points increase from baseline by Week 25 in the FACIT-Fatigue subscale score.The FACIT-Fatigue is a 13-item questionnaire that assesses participant reported fatigue and its impact upon daily activities and function over the past 7 days. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total scores from 0 (extreme fatigue) to 52 (no fatigue). Scores below 30 indicate severe fatigue.

OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.

As the median OS was not reached in any treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 54) are presented.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m\^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib + Rituximab

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m\^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo + Rituximab

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Open-Label Substudy: Ibrutinib

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.

Total

< 65 years old

>= 65 years old

Age, Customized

Lori Styles

Intent to Treat population: all randomized/enrolled participants

Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized

Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment.

Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized

Percentage of Participants With ≥ 3 Points Increase From Baseline by Week 25 in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Subscale Score

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors	NCT02403271	Non-Small Cell ... Breast Cancer Pancreatic Canc...	Ibrutinib Durvalumab	18 Years -	Pharmacyclics LLC.
Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)	NCT01236391	Mantle Cell Lym...	PCI-32765	18 Years -	Pharmacyclics LLC.
Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)	NCT03112174	Mantle-Cell Lym...	Ibrutinib Venetoclax Placebo Oral ta...	18 Years -	Pharmacyclics LLC.
Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia	NCT02165397	Waldenström's M...	Ibrutinib Placebo Rituximab	18 Years -	Pharmacyclics LLC.
Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia	NCT02165397	Waldenström's M...	Ibrutinib Placebo Rituximab	18 Years -	Pharmacyclics LLC.
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors	NCT02403271	Non-Small Cell ... Breast Cancer Pancreatic Canc...	Ibrutinib Durvalumab	18 Years -	Pharmacyclics LLC.

Spots Global Cancer Trial Database for pcyc

Every month we try and update this database with for pcyc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pcyc

Every month we try and update this database with for pcyc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pcyc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.