Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Tisagenlecleucel

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

Single-arm study investigating combination of ibrutinib and Tisagenlecleucel treatment

ibrutinib and Tisagenlecleucel

Michael Dickinson

This is an open label, multi-center, single-arm, phase II study investigating the efficacy and safety of the combination of ibrutinib and Tisagenlecleucel in twenty patients with relapsed or refractory Mantle Cell Lymphoma (MCL) or who had sub-optimal response to standard therapy in the presence of TP53 mutation.

Clinical Trial to Assess The Efficacy and Safety of the Combination of Tisagenlecleucel And Ibrutinib in Mantle Cell Lymphoma

A Phase II, Open-Label, Single Arm Trial to Assess The Efficacy and Safety of the Combination of Tisagenlecleucel And Ibrutinib in Mantle Cell Lymphoma

Through monitoring of the incidence, nature and severity of adverse events (graded according to NCI CTCAE v5.0), Serious Adverse Events, dose interruptions and dose reductions of ibrutinib

Measured through aggregate measure of peripheral blood/or bone marrow flow cytometry, PCR and ctDNA

By monitoring for patient death due to any cause

Novartis

Peter MacCallum Cancer Centre, Australia

Neoplasm Metastasis

Neoplastic Processes

Primary Central Nervous System Lymphoma

Micronutrients

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Vitamins

Leucovorin

Methotrexate

Rituximab

Vincristine

Lenograstim

Procarbazine

Tyramine

Immunologic Factors

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Folinic Acid

Folate

Vitamin B9

This is an open-label, non-randomized, single center, dose escalation, phase I/II study to establish the maximum-tolerated dose (MTD) of ibrutinib as a single agent in patients with refractory/recurrent PCNSL or refractory/recurrent SCNSL (Arm A).

The defined MTD from Arm A will then be used in an expansion cohort to further assess toxicity and clinical activity

Arm C will investigate the MTD of ibrutinib in combination with HD-MTX and to determine the safety and tolerability of the ibrutinib/HD-MTX combination regimen in PCNSL and SCNSL patients. To minimize drug-drug interaction between HD-MTX and Ibrutinib, Ibrutinib will not be administered concurrently with HD-MTX.

THIS IS ONLY ARM RECRUITING In Arm D, patients will be treated with 4 cycles of therapy. Methotrexate (3.5 g/m2) will be given at Dday 1 and Dday 15 of each cycle. Rituximab (500 mg/m2) will be given at Dday 0 and Dday 15 of each cycle. Vincristine (1.4mg/m2) will be given at Dday 1 and 15 of cycle 1 and 2 only. Procarbazine (100mg/m2) will be given of Day 1 of each cycle. Ibrutinib will be dosed at 560 mg daily. Arm D will have a safety lead-in of 6 patients. If more than 1 of 6 subjects develop a dose limiting toxicity (DLT) within the first 28 days of therapy (cycle 1), ibrutinib will be reduced to 420 mg daily dosing, and 6 additional patients will be enrolled. If more than 1 of 6 subjects develop a DLT, additional enrollment will be stopped.

Arm A: Ibrutinib will be given once daily. The starting dose cohort (level 1) will receive 560 mg/day (4 x 140 mg capsules). During the dose escalation period of the study, the "3+3" design will be applied (see Table 3). Participants will be assigned to cohorts of increasing oral daily doses of ibrutinib (560mg, 840mg) until disease progression, intolerable toxicity or death. Three patients with recurrent/refractory PCNSL or recurrent/refractory SCNSL will be treated with daily oral ibrutinib for a 28-day cycle starting at dose level 1 and observed for toxicities during cycle 1. Arm B: Ibrutinib will be given at the MTD defined in Arm A.

Arm C1: HD-MTX at 3.5g/m2 (standard hydration/leucovorin support) will be given on day 1 and 15 of each 28-day cycle for a total of 4 cycles totaling 8 HD-MTX administrations. Ibrutinib will be given between days 5 and 14 as well as days 19 and 28 of each cycle and continued daily after completion of HD-MTX treatments.The starting dose of ibrutinib is 560 mg/day (4x140mg capsules)

HD- Methotrexate (MTX)

Arm C2: Intravenous rituximab (500mg/m2) will be given on day 0, 14, and 28 of cycle 1 and day 14 and 28 of all following cycles. HD-MTX at 3.5g/m2 (standard hydration/leucovorin support) will be given on day 1 and 15 of each 28-day cycle for a maximum of 4 cycles totaling 8 HD-MTX administrations. Ibrutinib will be given between days 5 and 14 as well as days 19 and 28 of each cycle and continued daily after completion of HD-MTX treatments. The starting dose of ibrutinib is 560 mg/day (4x140mg capsules; dose level 1) (see Table 4). Filgrastim will be given at days 7-11 and 22-26.

Rituximab + HD- Methotrexate (MTX)

Arm D: THIS IS THE ONLY ARM RECRUITING: : Oral procarbazine (100mg/m2/day) will be given on Day 1 through 7 during each cycle. Patients will be maintained on a tyramine-free diet during procarbazine administration.

procarbazine

Christian Grommes, MD

Ingo Mellinghoff, MD

The purpose of this study is to test any good or bad effects of the study drug called of ibrutinib (also known as Imbruvica™). At this stage of this trial, the study is investigating whether Ibrutinib can be incorporated into the established first-line chemotherapy regimen rituximab, methotrexate, vincristine, and procarbazine (R-VMP) in order to further refine the first-line induction therapy for PCNSL, as observed by a superior CRR (complete response rate) (ARM D RECRUITING ONLY)

Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Patients With Newly Diagnosed or Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)

A Phase I/II Trial of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Patients With Newly Diagnosed or Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)

A standard 3+3 design will be employed. Three dose levels of ibrutinib will be investigated. Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A dose-limiting toxicity (DLT) is defined as in any of the following during cycle 1: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia associated with bleeding or any grade 3 non-hematologic toxicity that does not respond to supportive therapy and at least possibly related to treatment with ibrutinib.

Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause.

Three patients with PCNSL or SCNSL will be treated with daily oral ibrutinib +/- HD-MTX for a 28-day cycle starting at dose level 1 and observed for toxicities for a minimum of 4 weeks. Dose-limiting toxicity (DLT) will be defined as any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia associated with bleeding as well as any grade 3 non-hematologic toxicity that does not respond to supportive therapy and at least possibly related to ibrutinib. If no DLT is observed in any of the 3 treated patients, we will escalate to the next dose level.

in patients by assessing the frequency and severity of adverse events.

1. The severity grade (CTCAE Grade 1-4)
2. Its duration (Start and end dates)
3. Its relationship to the study treatment (Reasonable possibility that AE is related: No, Yes)
4. Action taken with respect to study or investigational treatment (none, dose adjusted, temporarily interrupted, permanently discontinued, unknown, ongoing, not applicable)

Duration of response is defined as the time from the date of first occurrence of CR or PR to the date of the first documented PD or death due to any cause.Duration of response will be described using Kaplan-Meier curves with appropriate summary statistics

Pharmacyclics LLC.

Janssen Biotech, Inc.

Memorial Sloan Kettering Cancer Center

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Hematologic Diseases

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chromosome 17p Deletion

Pembrolizumab

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Immune Checkpoint Inhibitors

Ibrutinib, Fludarabine, and Pembrolizumab combination therapy will be administered in participants with High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). Ibrutinib will be administered daily by mouth starting cycle -3 at 420 mg until end study or disease progression or intolerable side effects occur. Fludarabine will be administered intravenously only on cycle -2 at 25mg/m\^2 x5 days. Pembrolizumab will be administered intravenously every 3 weeks at 200 mg starting from cycle 1 through cycle 17 or 1 year of immunotherapy phase.

Ibrutinib will be administered daily by mouth starting cycle -3 at 420 mg until end study or disease progression or intolerable side effects occur.

Fludarabine will be administered intravenously only on cycle -2 at 25mg/m\^2 x5 days.

Pembrolizumab will be administered intravenously every 3 weeks at 200 mg starting from cycle 1 through cycle 17 or 1 year of immunotherapy phase.

Adrian U Wiestner, M.D.

Background:

Chronic lymphocytic leukemia and small lymphocytic lymphoma (hereby referred as CLL) are tumors of B cells. A subset of patients categorized as high-risk CLL has a poor clinical outcome when treated with conventional chemotherapy. This single-arm, phase II study investigates the combination of ibrutinib, fludarabine and pembrolizumab for treatment of CLL. Ibrutinib is an orally administered therapy for CLL. Fludarabine is a well-tolerated drug that has been widely used to treat CLL. Also, fludarabine can modulate CLL cells as well as immune cells that support the growth of CLL cells. Pembrolizumab recruits immune cells to attack CLL cells. With this approach we hope to achieve a greater reduction in CLL cells than with single agent ibrutinib and to restore healthier immune system that could contribute to durable responses.

Objective:

To investigate the rate of complete response to ibrutinib, short course fludarabine and pembrolizumab.

Eligibility:

Patients with active CLL meeting treatment indications defined by 2008 International Workshop on CLL (IWCLL) consensus guideline.

High-risk CLL defined by one of the following:

* Relapsed/refractory disease status, or
* Presence of high-risk mutations regardless of prior treatment status: deletion 17p, TP53 mutation, NOTCH1 mutation, SF3B1 mutation, MYC aberration, or complex cytogenetics.

Design:

This is a single-arm, open-label phase II study.

Timeline: Treatment on this study is given in cycles from cycle -3 to 17, then in months beyond cycle 17. Cycles -3 to -1 are 28-day cycles. Cycles 1 to 17 are 21-day cycles. After completion of 1 year of pembrolizumab, the time on study is by chronological months on study from starting pembrolizumab.

Treatment plan:

* Ibrutinib is given starting from cycle -3 and continuously until disease progression or intolerable side effects occur.
* Fludarabine is given on D1-D5 on cycle -2 only
* Pembrolizumab is given every 3 weeks starting from cycle 1 for 1 year.
* Minimal residual disease will be measured at 2 years from cycle 1 to determine the need for long- term treatment with ibrutinib.

  * Previously-untreated patients who achieve minimal residual disease negativity will stop ibrutinib.
  * Patients who do not achieve minimal residual disease negativity or who has Relapsed/refractory CLL will continue ibrutinib.

Background:

This study investigates the combination of ibrutinib, fludarabine and pembrolizumab for treatment of CLL. Chronic lymphocytic leukemia and small lymphocytic lymphoma (hereby referred as CLL) are tumors of B cells. A subset of patients categorized as high-risk CLL has a poor clinical outcome when treated with conventional chemotherapy. High-risk CLL is defined by relapsed/refractory disease status, or the presence of high-risk mutations, such as deletion 17p, TP53, and NOTCH1. While the cause of CLL is still unclear, studies have indicated critical factors required for the tumor cells. First, CLL cells grow and survive because they receive signals through the B-cell receptor (BCR); and second, CLL cells benefit from interactions with other cells, especially T cells.

The stimulation through the BCR can be blocked by ibrutinib, which is an oral drug that selectively inhibits Bruton's tyrosine kinase (BTK). In clinical trials, ibrutinib demonstrated safety and high response rates in patients with high-risk disease. Ibrutinib has gained FDA approval as a treatment for CLL regardless of prior treatment or cytogenetic status. However, single-agent ibrutinib has limitations; the drug does not eliminate all tumor cells and, with time, the tumor cells may become resistant. Therefore, combination of ibrutinib with other drugs could be beneficial.

Objectives:

-To investigate the rate of complete response to ibrutinib, short course fludarabine and pembrolizumab.

Key eligibility criteria:

Patients with active CLL meeting treatment indications defined by 2008 International Workshop on CLL (IWCLL) consensus guideline.

High-risk CLL defined by one of the following:

Relapsed/refractory disease status, or

Presence of high-risk mutations regardless of prior treatment status: deletion 17p, TP53 mutation, NOTCH1 mutation, SF3B1 mutation, MYC aberration, or complex cytogenetics.

Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase II Study Of Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Rate of complete response with combination ibrutinib, fludarabine, and pembrolizumab in patients with high-risk and/or relapsed/refractory chronic lymphocytic leukemia and small lymphocytic leukemia. Response assessments defined by IWCLL 2008 guidelines incorporating the 2012 and 2013 clarifications for patients treated with kinase inhibitors. Complete response defined as: Lymphadenopathy is none \> 1.5 cm; No Splenomegaly or Hepatomegaly; Blood Lymphocytes \<4000/uL; Bone Marrow is normocellular, \<30% lymphocytes, no B-lymphoid nodules; Platelet count \>100,000/uL; Hemoglobin \> 11.0 g/dL and Neutrophils \>1500/uL. Partial response is defined by meeting 2 criteria: Lymphadenopathy decrease \> or = 50%; Splenomegaly or Hepatomegaly decrease \> or = 50%; Blood Lymphocytes decrease \> or = 50% from baseline; Platelet is \> 100,000/uL or increase \> or = 50% over baseline; Hemoglobin is \> 11.0 g/dL or increase \> or = 50% over baseline; Neutrophils is \> 1500/uL or increase \> or = 50% over baseline.

Tolerability of the combination regimen, Overall response rate (ORR), Duration of response (DOR), Best response, Minimal residual disease (MRD) status, Progression-free survival (PFS), Overall survival (OS), To explore the biologic effects on B- and T-cell subsets and function, To identify predictors of clinical response.

National Heart, Lung, and Blood Institute (NHLBI)

Ibrutinib, Fludarabine, and Pembrolizumab in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Adrian Wiestner, M.D., Ph.D., Principal Investigator

Includes all participants that completed the 1 year evaluation

Number of Participants With Complete Response of the Combination of Ibrutinib, Fludarabine, and Pembrolizumab in Patients With High-risk and/or Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia

Tolerability, Response and Best Response, Survival

Conditioning Phase (12 Weeks)

Immunotherapy Phase (1 Year)

Follow-up Phase (Extension Study)

Tislelizumab

Zanubrutinib

All participants to receive open-label zanubrutinib

Participants to receive the combination as in the parent study (Australia Only)

Participants will receive zanubrutinib at a dose of 160 mg twice daily (for a total daily dose of 320 mg), or the last dose level received in the BeiGene parent study.

Patients in Australia who participated in a parent study that involved combination therapy of zanubrutinib and tislelizumab will receive tislelizumab at a dose of 200mg every 3 weeks..

BeiGene

Study Director

The purpose of this study is to evaluate the long-term safety of zanubrutinib regimens in participants with B-cell malignancies who participated in a BeiGene parent study for zanubrutinib.

Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Participants With B-cell Malignancies

An Open-label, Multi-center, Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Patients With B-cell Malignancies

Safety as assessed by incidence of all treatment-emergent adverse events (TEAEs) and serious AEs (SAEs)

Time from the starting date of zanubrutinib in the eligible BeiGene study to the date of first documentation of disease progression or death, whichever occurs first

Time from the date that response criteria are first met after the start of zanubrutinib in the eligible BeiGene study to the date that progressive disease (PD) is objectively documented or death, whichever occurs first

Time from the starting date of zanubrutinib in the eligible BeiGene study to the date of death due to any reason

Lymphoma, Large B-Cell, Diffuse

Diffuse Large B-Cell Lymphoma

Phase 1 will evaluate itacitinib at the protocol-specified starting dose, with a possible increase or decrease depending on tolerability. Phase 2 will evaluate the recommended dose determined in Phase 1.

itacitinib

ibrutinib

Peter Langmuir, MD

The purpose of this study is to evaluate the safety/tolerability and efficacy of itacitinib in combination with ibrutinib in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

An Open-Label Phase 1/2 Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated.

A DLT was defined as the occurrence of any protocol-defined toxicities occurring up to and including Study Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria. In order to be included in the tolerability review, subjects must have received the cohort-specific dose of INCB039110 and ibrutinib for at least 75% of the days during the 28-day surveillance period or have experienced a DLT.

CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 centimeters (cm) in the longest dimension transverse diameter of lesion (LDi); (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: ≥50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 millimeters (mm) × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node \>5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by \>50% in length beyond normal; (4) no new lesions.

CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 cm in the LDi; (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: ≥50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 mm × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node \>5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by \>50% in length beyond normal; (4) no new lesions.

Disease progression requires ≥1 of the following: (1) an abnormal individual node/lesion with all of the following: (a) LDi \> 1.5 cm; (b) increase by ≥50% from cross product of the LDi and the perpendicular diameter (PPD) nadir; (c) increase in LDi or the shortest axis perpendicular to the LDi (SDi) from nadir: (i) 0.5 cm for lesions ≤2 cm; (ii) 1.0 cm for lesions \> 2 cm. (2) For splenomegaly, the splenic length must increased by 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, must increase by at least 2 cm from baseline. (3) New/recurrent splenomegaly. (4) New/clear progression of preexisting nonmeasured lesions. (5) Regrowth of previously resolved lesions. (6) A new node \> 1.5 cm in any axis. (7) A new extranodal site \> 1.0 cm in any axis; if \< 1.0 cm in any axis, its presence must be unequivocal/attributable to lymphoma. (8) Assessable disease of any size unequivocally attributable to lymphoma. (9) New or recurrent involvement of the bone marrow.

DRR=percentage of participants with a CR or PR, per Lugano Classification, for ≥16 weeks since the time from the first overall response contributing to an objective response (CR or PR). CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 cm in the LDi; (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: ≥50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 mm × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node \>5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by \>50% in length beyond normal; (4) no new lesions.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated.

Incyte Corporation

Treatment-emergent adverse events (AEs reported for the first time or the worsening of pre-existing AEs after the first dose and until 30 days after the last dose of study drug) are reported for members of the Phase 1 Safety Run-In Population and the Phase 2 Safety Evaluable Population (all enrolled participants who received ≥1 dose of study drug).

Participants received oral itacitinib 300 milligrams (mg) once daily (QD) plus oral ibrutinib 560 mg QD until treatment discontinuation criteria were met.

Phase 1; Cohort 1: Itacitinib 300 mg QD + Ibrutinib 560 mg QD

Participants in Cohort 2 of Phase 1 and in Phase 2 received oral itacitinib 400 mg QD plus oral ibrutinib 560 mg QD until treatment discontinuation criteria were met.

Phases 1 and 2: Itacitinib 400 mg QD + Ibrutinib 560 mg QD

Total

Participants received oral itacitinib 400 mg QD plus oral ibrutinib 560 mg QD until treatment discontinuation criteria were met.

Phase 1; Cohort 2: Itacitinib 400 mg QD + Ibrutinib 560 mg QD

Phase 2: Itacitinib 400 mg QD + Ibrutinib 560 mg QD

Age, Continuous

White/Caucasian

Black/African-American

Asian

Captured as "Other"

Missing

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Not Reported

Unknown

In Phase 1, Baseline data were collected for members of the Safety Run-In Population, defined as all participants enrolled in the Phase 1 portion of the study who received at least 1 dose of study drug. In Phase 2, Baseline data were collected for members of the Intent-to-Treat Population, defined as all participants enrolled in the Phase 2 portion of the study.

Safety Run-In Population: all participants enrolled in the Phase 1 portion of the study who received at least 1 dose of study drug

Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

Phase 1: Number of Participants With Any Grade 3 or Higher TEAE

Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)

Intent-to-Treat (ITT) Population: all participants enrolled in the Phase 2 portion of the study. The confidence interval was calculated based on the exact method for binomial distribution.

Phase 2: Objective Response Rate (ORR), Defined as the Percentage of Participants Achieving Either a Complete Response (CR) or a Partial Response (PR), Per the Modified Lugano Classification for Diffuse Large B-cell Lymphoma (DLBCL)

Safety Run-in Population. The confidence interval was calculated based on the exact method for binomial distribution.

Phase 1: ORR, Defined as the Percentage of Participants Achieving Either a CR or a PR, Per the Modified Lugano Classification for DLBCL

ITT Population. Participants who achieved a CR or a PR per Lugano Classification for DLBCL were analyzed. The 90% confidence interval was calculated using the Brookmeyer and Crowley's method.

Phase 2: Duration of Response (DOR): Time From the First Overall Response Contributing to an Objective Response (CR or PR) to the Earlier of the Participant's Death and the First Overall Response of Progressive Disease, Per the Lugano Classification

ITT Population. Participants who achieved a CR or a PR per Lugano Classification were analyzed. The confidence interval was calculated based on the exact method for binomial distribution.

Phase 2: Durable Response Rate (DRR)

ITT Population. The 90% confidence interval was calculated using the Brookmeyer and Crowley's method.

Phase 2: Progression-free Survival (PFS), Defined as the Time From the First Dose to the Earlier Date of Death Due to Any Cause or Disease Progression Determined by Objective Radiographic Disease Assessments

Safety Evaluable Population: all participants enrolled in the Phase 2 portion of the study who received at least 1 dose of study drug

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial to Assess The Efficacy and Safety of the Combination of Tisagenlecleucel And Ibrutinib in Mantle Cell Lymphoma	NCT04234061	Mantle Cell Lym...	ibrutinib and T...	18 Years -	Peter MacCallum Cancer Centre, Australia
Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Patients With Newly Diagnosed or Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)	NCT02315326	Adult Patients ... Or Relapsed or ...	Ibrutinib HD- Methotrexat... Rituximab + HD-... procarbazine	18 Years -	Memorial Sloan Kettering Cancer Center
Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	NCT03204188	B-Cell Chronic ... B-Lymphocytic L... Chronic Lymphoc... Leukemia, Chron... Leukemia, Chron... Leukemia, Lymph... Leukemia, Lymph... Lymphocytic Leu... Lymphocytic Leu...	Ibrutinib Fludarabine Pembrolizumab	18 Years -	National Institutes of Health Clinical Center (CC)
Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Participants With B-cell Malignancies	NCT04170283	B-cell Malignan...	Zanubrutinib Tislelizumab	18 Years -	BeiGene
A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma	NCT02760485	Lymphoma	itacitinib ibrutinib	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for bruton's tyrosine kinase (btk) inhibitor