Symptoms and General Pathology

All Conditions

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Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

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Leukemia, Myeloid, Acute

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Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Lymphosarcoma

MLL-r and MLL-PTD 28-day continuous IV infusion of each 28-day cycle. Number of cycles: until disease progression or unacceptable toxicity develops.

EPZ-5676

Martin S. Tallman, MD

Jesus Berdeja, MD

David A Rizzieri, MD

Guillermo Garcia-Manero, MD

Jessica Altman, MD

Raoul Tibes, MD

Mojca Jongen-Lavrencic, MD

Hartmut Döhner, MD

Ipsen Medical Director

The purpose of this study is to determine the safe dose of EPZ-5676, to evaluate the safety of EPZ-5676 in patients with advanced hematologic malignancies, and to conduct a preliminary assessment of the anti-leukemia activity of EPZ-5676 in patients with acute leukemias bearing rearrangements of the MLL gene.

Currently this study is in the MLL-r restricted/expansion phase and is only enrolling patients with rearrangements involving the MLL gene, including 11q23 or partial tandem duplications (PTD).

A subset of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) harbor rearrangements of the MLL gene, which are detected either by cytogenetic or fluorescent in situ hybridization evaluation at the time of diagnosis. A protein called DOT1L plays an important role in the malignant process in these leukemias. EPZ-5676 is a molecule that blocks the activity of DOT1L, and is therefore being evaluated in the treatment of patients with MLL-rearranged leukemias.

The dose escalation portion has been completed. Currently this study is in the expansion phase and patients with MLL-r and MLL-PTD will receive EPZ-5676 as a 28-day continuous intravenous infusion (CIV).

A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving

A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving Translocation of the MLL Gene at 11q23 or Advanced Hematologic Malignancies

The MTD is defined as the dose level below in which \>1 patient out of 3 or \>2 patients out of 6 experience dose-limiting adverse events (as defined by the protocol).

analysis of Cmax, AUC and steady state concentration

Evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments

Evaluation of response by standard criteria for AML or ALL

Celgene

Epizyme, Inc.

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Carcinoma

Lymphoma, Large B-Cell, Diffuse

Sarcoma

Lymphoma, Follicular

Mesothelioma

Mesothelioma, Malignant

Lymphoma, B-Cell

Carcinoma, Medullary

Sarcoma, Synovial

Rhabdoid Tumor

Lymphoma, Non-Hodgkin

Neoplasms, Connective and Soft Tissue

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Neoplasms, Connective Tissue

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Soft Tissue Sarcoma

Follicular Lymphoma

Malignant Mesothelioma

Thyroid Cancer, Medullary

Renal Medullary Carcinoma

Synovial Sarcoma

Epithelioid Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Itraconazole

Rifampin

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Participants in Part 1 of the study will receive a single oral, 400 mg dose of tazemetostat on Day 1, 15, and Day 36.

The study participants will receive tazemetostat (oral 400 mg) tablets to be taken twice daily on Days 3 - 14 and Days 21 - 35. In addition, the participants will receive oral 200 mg itraconazole once daily on Days 18 - 38.

Study participants may continue tazemetostat from Day 40+ at the recommended therapeutic dose (oral 800 mg twice daily) in 28-day cycles.

Participants in Part 2 of the study will receive a single oral, 800 mg dose of tazemetostat on Days 1, 15, and Day 36.

The study participants will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily on Days 3 - 14 and Days 17 - 23. In addition, the participants will receive oral 200 mg rifampin once daily on Days 17 - 25.

Study participants may continue tazemetostat from Day 27+ at the recommended therapeutic dose (oral 800 mg twice daily) in 28-day cycles.

A single, oral, 400 mg dose of tazemetostat on Day 1, Day 15, and Day 36; and tazemetostat (oral 400 mg) tablets twice daily on Days 3 - 14 and Days 21 - 35.

Tazemetostat

Oral 200 mg itraconazole once daily on Days 18 - 38

A single, oral, 800 mg dose of tazemetostat on Days 1, 15, and Day 24 ; and tazemetostat (oral 800 mg) twice daily on Days 3 - 14 and on Days 17 - 23.

Oral 600 mg rifampin once daily on Days 17 - 25.

Ipse Medical Director

The participants of this study will have advanced malignancies (also known as advanced cancer). The main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the tazemtostat (the study drug) when administered in combination with another drug.

Part 1 of the study will evaluate the interaction between the drugs tazemetostat and itraconazole.

Part 2 of the study will evaluate the interaction between the drugs tazemetostat and rifampin

For both Parts 1 and 2, safety and the level that effects of the study drug can be tolerated (known as tolerability) will be assessed throughout.

This two-part study is designed to characterize the steady-state PK of oral tazemetostat and its metabolite EPZ 6930 when administered as a single and twice daily dose in subjects with advanced malignancies while taken alone or in combination with either itraconazole or rifampin.

Part 1: tazemetostat and Itraconazole Drug Interaction Part 1 of the study will evaluate the drug-drug interaction between tazemetostat and itraconazole in an open-label, fixed sequential cross over design.

Part 2: tazemetostat and Rifampin Drug Interaction Part 2 of the study will evaluate the drug-drug interaction between tazemetostat and rifampin in an open-label, fixed sequential cross over design.

For both Parts 1 and 2, safety and tolerability will be assessed throughout the subject's participation. Subjects must have an end of study visit after 30 days of the last dose of tazemetostat for safety assessment.

Study to Describe the Interaction Between Tazemetostat and Itraconazole and Between Tazemetostat and Rifampin in Participants With Advanced Cancer

A Phase I, Open-label Multi-dose Two-part Study to Characterize the Effects of a Strong CYP3A4 Inhibitor and a Strong CYP3A4 Inducer on the Steady-State Pharmacokinetics of Tazemetostat (EPZ-6438) in Subjects With Advanced Malignancies

Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of tazemetostat will be evaluated by the Investigator based on the CTCAE, version 5.0.

Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator.

Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be decided by the investigator.

Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.

ECOG is a 4-point performance status scale used to assess performance as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 4 = Completely disabled). Performance status will be assessed per usual clinical practice and will be recorded in the medical record.

All prior medications administered 30 days before study drug administration will be recorded.

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Antineoplastic Agents, Hormonal

Patients in the Phase 1 portion of the study.

Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.

Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.

Patients with R/R DLBCL treated with tazemetostat as a single agent or tazemetostat in combination with prednisolone in Phase 2 of the study.

Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Patients who received 40 mg/m\^2 prednisolone once daily on Days 1-5 and 15-19 of Cycles 1-4.

Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.

This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas and tazemetostat in combination with prednisolone in subjects with diffuse large B-cell lymphoma (DLBCL).

This is a multicenter, open-label, Phase 1/2 study conducted in two parts: The Phase 1 part comprised dose escalation and expansion to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) when tazemetostat was given twice daily (BID) orally on a continuous basis. Additionally, in separate cohorts in Phase 1, the effect of food on the bioavailability of tazemetostat as well as the drug-drug interaction (DDI) potential of tazemetostat were evaluated. The Phase 2 part was initiated once the RP2D was established. Phase 2 enrolled subjects with relapsed/ refectory (R/R) DLBCL (Cohorts 1-3 and 6) and subjects with R/R FL (Cohorts 4 and 5) for the determination of efficacy and safety of tazemetostat monotherapy (Cohorts 1-5) and of tazemetostat in combination with prednisolone (Cohort 6) with placement determined by centrally confirmed histology, cell of origin (COO), and enhancer of zeste homologue 2 (EZH2) mutation status.

Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL

An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma

Recommended Phase 2 dose (RP2D) of tazemetostat as administered orally twice daily (BID), continuously in 28-day cycles in subjects with advanced solid tumors or with relapsed and/or refractory B cell lymphomas as determined by incidence, seriousness, toxicity grade, and relatedness of treatment emergent dose limiting toxicities

Number of patients achieving an objective response (CR or PR)/number of patients treated x 100%. ORR was calculated as the percentage of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of patients in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

The time (in months) from the date of the initial response (CR or PR, whichever was first) until the date of the first documented disease progression per an Independent Review Committee (for Groups 1 and 2), per Investigator (Group 3), or death due to any cause. Patients who were alive and progression free at the time of the analysis were censored at the last date where the patient was known to be in response. Note: the DOR was censored, meaning data collection was stopped early for analysis, making the top limit of the 95% confidence interval not estimable (NE). Per RECIST v.1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

The time (in months) from the date of first dose of tazemetostat until the earliest date of disease progression or death from any cause. Per RECIST v1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

The safety population included all patients in the Intent-to-treat (ITT) population set who had at least 1 post-dose safety observation recorded. MedDRA v17.1 for Phase 1 and MedDRA v18.1 for Phase 2.

Patients received tazemetostat 100 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 100 mg

Patients received tazemetostat 200 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 200 mg

Patients received tazemetostat 400 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 400 mg

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 800 mg

Patients received tazemetostat 1600 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 1600 mg

Patients received tazemetostat 200 mg as a single oral dose on Day -8 either after fasting for 8 hours before dosing or immediately after consuming a high-fat breakfast on Day -8. Following a 7-day washout period, patients crossed over to receive the second tazemetostat 200 mg single oral dose on Day -1 in the opposite condition (fed or fasted).

Phase 1: Food Effect (All Patients)

Patients received tazemetostat 800 mg orally BID continuously starting on Day 1, with a single oral dose of midazolam 2 mg administered on Day -1 and then on Day 15. Post Day 15, patients continued to receive tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 800 mg + Midazolam 2 mg

Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 1: Tazemetostat in R/R FL With Mutant EZH2

Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 2: Tazemetostat in R/R FL With Wild-Type EZH2

Patients with R/R DLBCL received 800 mg of tazemetostat monotherapy, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 3: Tazemetostat in R/R DLBCL Monotherapy

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. In addition, these patients also received prednisolone 40 mg/m\^2 on Days 1 to 5 and 15 to 19 from Cycle 1 to Cycle 4 post which tazemetostat monotherapy was continued.

Phase 2 Group 4: Tazemetostat + Prednisolone in R/R DLBCL Combination Therapy

Patients received tazemetostat 200 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent

Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Tazemetostat: Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Tazemetostat: Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Patients with R/R DLBCL received 800 mg of tazemetostat monotherapy, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Tazemetostat: Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Lead or Designee

Patients in the Phase 1 portion of the study. Tazemetostat: Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Phase 1

Recommended Phase 2 Dose (RP2D) of Tazemetostat as a Single-Agent and in Combination With Prednisolone (Phase 1 Only)

Objective Response Rate (ORR; Complete Response + Partial Response [CR + PR]) (Phase 2)

Phase 2 Group 4: Tazemetostat + Prednisone in R/R DLBCL Combination Therapy

Patients who had a complete or partial response per an Independent Review Committee. Note: the DOR for some patients was censored, meaning data collection was stopped early for analysis making the top limit of the 95% confidence interval not estimable.

Duration of Response for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)

Patients who had a response event per Independent Review Committee.

Progression Free Survival for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)

Patients received tazemetostat 100 milligrams (mg) tablets orally twice daily (BID) in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Patients with R/R FL with mutant enhancer of zeste homolog 2 (EZH2) treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 1: Tazemetostat in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) With Mutant EZH2

Phase 2 Group 3: Tazemetostat in R/R Diffuse Large B-cell Lymphoma (DLBCL) Monotherapy

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. In addition, these patients also received prednisolone 40 mg/meter square (m\^2) on Days 1 to 5 and 15 to 19 from Cycle 1 to Cycle 4 post which tazemetostat monotherapy was continued.

Overall Study

EPZ-5676 Dose escalation and expansion cohorts

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving	NCT01684150	Acute Myeloid L... Acute Lymphobla... Myelodysplastic... Myeloproliferat...	EPZ-5676	18 Years - 90 Years	Ipsen
Study to Describe the Interaction Between Tazemetostat and Itraconazole and Between Tazemetostat and Rifampin in Participants With Advanced Cancer	NCT04537715	All Malignancie... Advanced Malign... Hematologic Mal... Solid Tumor Follicular Lymp... Non-Hodgkin Lym... Diffuse Large B... Epithelioid Sar... Synovial Sarcom... Renal Medullary... Mesothelioma Rhabdoid Tumor	Tazemetostat Itraconazole Tazemetostat Rifampin	18 Years -	Ipsen
Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL	NCT01897571	B-cell Lymphoma... Advanced Solid ... Diffuse Large B... Follicular Lymp... Transformed Fol... Primary Mediast...	Tazemetostat Prednisolone Tazemetostat	16 Years -	Ipsen
A Phase 1 Dose Escalation and Expanded Cohort Study of EPZ-5676 in the Treatment of Pediatric Patients With Relapsed/Refractory Leukemias Bearing a Rearrangement of the MLL Gene	NCT02141828	Leukemia Acute Myeloid L... Acute Lymphocyt... Acute Leukemias	EPZ-5676	3 Months - 18 Years	Ipsen
Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL	NCT01897571	B-cell Lymphoma... Advanced Solid ... Diffuse Large B... Follicular Lymp... Transformed Fol... Primary Mediast...	Tazemetostat Prednisolone Tazemetostat	16 Years -	Ipsen
A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving	NCT01684150	Acute Myeloid L... Acute Lymphobla... Myelodysplastic... Myeloproliferat...	EPZ-5676	18 Years - 90 Years	Ipsen
A Study to Assess the Long-term Safety of Tazemetostat	NCT02875548	Diffuse Large B... Follicular Lymp... Synovial Sarcom... Epitheliod Sarc... Mesothelioma Advanced Solid ... Renal Medullary... Non-Hodgkin Lym...	Tazemetostat	18 Years -	Ipsen

Spots Global Cancer Trial Database for epizyme

Every month we try and update this database with for epizyme 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 epizyme

Every month we try and update this database with for epizyme 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 epizyme 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.