Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Amino Acids

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Lenalidomide

Etoposide phosphate

Ibrutinib

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R

Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R

Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

DA-EPOCH-R

Jutta Neuenburg, MD

This is a Phase 1b/2, open-label, non-randomized multicenter study to assess the safety and efficacy of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).

This is a Phase 1b, open-label, non-randomized multicenter study conducted in 2 parts. Part 1, will determine the MTD of the combination of ibrutinib, lenalidomide and DA-EPOCH-R in subjects with DLBCL.

Ibrutinib will be administered at a fixed dose of 560 mg and lenalidomide will be dose-escalated. DA-EPOCH-R will be given at standard doses.

For Part 2, the MTD determined in Part 1 will be the dose used for all subjects. If no MTD is identified, then subjects in Part 2 will be treated with the maximum administered doses (MAD, treatment doses from dose Level 4).

The primary objective for Part 2 is to determine the ORR of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with ABC DLBCL as analyzed by gene expression profiling when treated at recommended phase 2 dose (RP2D).

Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma

A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R

Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator.

Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator.

Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.

Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology.

Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented.

Celgene Corporation

Pharmacyclics LLC.

Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 0 (PO)

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 1: Dose Level 1

Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 15 (PO)

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 1: Dose Level 2

Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 20 (PO)

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 1: Dose Level 3

Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 25 mg (PO)

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 1: Dose Level 4

Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

All Subjects Treated at RP2D

Ibrutinib 560 mg PO + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 2: RP2D

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Director of Clinical Operations

Ibrutinib 560 mg (PO) +lenalidomide 0,15, 20, and 25 mg (PO) + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 1: All Treated

Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability

Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Note: There are only 17 samples available for DLBCL subtype test per GEP. Among of them 14 subjects were identified with ABC.

ABC Subjects Treated at RP2D

Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR

Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy

Number of Subjects With Adverse Events as a Measure of Safety and Tolerability

Progression Free Survival (PFS)

Overall Survival (OS)

Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Note: There are only 17 samples available for DLBCL subtype test per GEP. Among them 14 subjects were identified with ABC.

Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy

All Subjects Treated at RP2D Who Achieved Overall Response

ABC Subjects Treated at RP2D Who Achieved Overall Response

Duration of Response (DOR)

Overall Study

Symptoms and General Pathology

Digestive System Diseases

Gland and Hormone Related Diseases

Neoplasm Metastasis

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gemcitabine

Antimetabolites

Subjects receive Gemcitabine 1000 mg/m2 weekly intravenous infusion.

Part A: Subjects received PCI-27483 0.8 mg/kg BID as initial dose and may be escalated to 1.2, and 1.5 mg/kg BID. At the same time, subjects received Gemcitabine 1000 mg/m2 weekly intravenous infusion.

Part B: Subjects received the PCI-27483 at 1.2 mg/kg BID and Gemcitabine 1000 mg/m2 weekly intravenous infusion.

Part A: Closed to enrollment.Part B: Approximately 20 patients will be randomized to the control arm that will receive a standard regimen of gemcitabine and 20 patients will be randomized to the PCI-27483 arm and treated with both gemcitabine and PCI-27483. PCI-27483 will be administered as subcutaneous (SC) injections, nominally at a dosage of 1.2 mg/kg BID. Patients receiving PCI-27483 with a tumor response or stable disease at 12 weeks will have the option to continue PCI-27483 treatment until disease progression or the investigator considers the study treatment no longer tolerable. Treatment with gemcitabine may continue per standard of care.

All evaluable patients will roll over into Part C at week 16 (Day 113±5). If 2 consecutive INRs at 2 hours postdose are \>3.50,a reduced dosage will be calculated.

PCI-27483

Eric Hedrick, MD

Laurence Elias, MD

The purpose of this study is to evaluate the safety and tolerability of selected dose 1.2mg/kg BID dosage administered subcutaneously (SC) administered PCI-27483 to metastatic or locally advanced pancreatic cancer patients receiving concurrent therapy with intravenously administered gemcitabine for 12 weeks.

This study will be conducted in three segments: Part A, Part B and Part C. Parts A and B are 12 weeks of treatment followed by 4 weeks of evaluation. In part A patients will dose-escalate up to three dose levels of PCI-27483 administered as subcutaneous (SC) injections twice-daily (BID). Part B to start once 4th patient completes 90 of 112 doses in 8 weeks. In part B patients are randomized to PCI-27483 and gemcitabine (active arm) OR gemcitabine only (control arm). PCI-27483 doses in both Part A and B will be administered in combination with a standard regimen of gemcitabine. Patients with a tumor response or stable disease at 12 weeks will have the opportunity to continue PCI-27483 treatment until disease progression or the Investigator considers the study treatment to be no longer tolerable. Treatment with gemcitabine in either the active or control arm may continue until a standard course of gemcitabine therapy has been completed. Patients will complete Part A or Part B after 16 weeks on study regardless of treatment duration. Evaluable patients will roll over into part C and be followed for 12 months from enrollment (first dose).

Study of Safety and Tolerability of PCI-27483 in Patients With Pancreatic Cancer Patients Receiving Treatment With Gemcitabine

Phase II Study of Coagulation Factor VIIa Inhibitor PCI-27483 in Pancreatic Cancer Patients Receiving Treatment With Gemcitabine

Clinically meaningful toxicity adverse events will be defined in accordance with by CTCAE v3.0

Part A is a nonrandomized dose escalation arm. Subjects received PCI-27483 0.8 mg/kg BID as initial dose and may be escalated to 1.2, and 1.5 mg/kg BID. At the same time, patients received Gemcitabine 1000 mg/m2 weekly intravenous infusion on 3 out of every 4 weeks.

All treated subjects in this group experienced at least one "treatment-emergent" adverse event.

(PCI-27483 + Gemcitabine)/Part A

Part B is a randomized arm to evaluate safety and efficacy. Patients received PCI-27483 at 1.2 mg/kg BID and Gemcitabine 1000 mg/m2 weekly intravenous infusion.

All treated subjects in this group experienced at least one "treatment-emergent" adverse event.

(PCI-27483 + Gemcitabine)/Part B

Patients in this arm of Part B received Gemcitabine 1000 mg/m2 weekly intravenous infusion.

All treated subjects in this group experienced at least one "treatment-emergent" adverse event.

Gemcitabine/Part B

Dr. Laurence Elias

Number of Participants With Treatment Emergent Adverse Events (AEs)

Part A is a nonrandomized dose escalation arm. Subjects received PCI-27483 0.8 mg/kg BID as initial dose and may be escalated to 1.2, and 1.5 mg/kg BID. At the same time, subjects received Gemcitabine 1000 mg/m2 weekly intravenous infusion on 3 out of every 4 weeks.

PCI-27483 + Gemcitabine/Part A

Part B is a randomized arm to evaluate safety and efficacy. Subjects received PCI-27483 at 1.2 mg/kg BID and Gemcitabine 1000 mg/m2 weekly intravenous infusion.

PCI-27483 + Gemcitabine/Part B

Subjects in this arm of Part B received Gemcitabine 1000 mg/m2 weekly intravenous infusion.

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Breast 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

Atezolizumab

Immunomodulating Agents

Durvalumab

Antineoplastic Agents, Immunological

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.

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.

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

Lymphoma, Mantle-Cell

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma	NCT02142049	Diffuse Large B... Diffuse Large B...	Ibrutinib DA-EPOCH-R Lenalidomide	18 Years -	Pharmacyclics LLC.
Study of Safety and Tolerability of PCI-27483 in Patients With Pancreatic Cancer Patients Receiving Treatment With Gemcitabine	NCT01020006	Pancreatic Canc... Ductal Adrenoca... Exocrine Pancre...	PCI-27483 Gemcitabine	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.
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.
Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma	NCT02142049	Diffuse Large B... Diffuse Large B...	Ibrutinib DA-EPOCH-R Lenalidomide	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.
Study of Safety and Tolerability of PCI-27483 in Patients With Pancreatic Cancer Patients Receiving Treatment With Gemcitabine	NCT01020006	Pancreatic Canc... Ductal Adrenoca... Exocrine Pancre...	PCI-27483 Gemcitabine	18 Years -	Pharmacyclics LLC.

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