Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

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

Gemcitabine

Oxaliplatin

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

A-RGEMOX regimen (21 days per cycle, A total of 6 cycles) :

Allotinib: 12mg d1\~14 po qd, Rituximab: 375mg/m2 d1, gemcitabine: 1000mg/m2 d1 and d8, oxaliplatin: 130mg/m2 d1

Anlotinib: 12mg d1\~14 po qd, Rituximab: 375mg/m2 d1, gemcitabine: 1000mg/m2 d1 and d8, oxaliplatin: 130mg/m2 d1;

For subjects ≥75 years of age, appropriate reduction of chemotherapy drugs (not less than 75% of the standard dose, or withdrawal of day 8 gemcitabine) may be decided by the investigator.

Anlotinib hydrochloride, Rituximab, gemcitabine, oxaliplatin

Xi Chen

Haiyan Yang

Haiyan Yang, PhD

Xi Chen, MD

As the most common subtype of lymphoma, diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. However, patients with early relapse (relapse within 12 months since diagnosis or the end of first-line treatment, ER) or primary refractory had an even worse prognosis. Thus, the investigators plan to evaluate the efficacy and safety of anlotinib combined with rituximab, gemcitabine, oxaliplatin (A-RGEMOX) in the treatment of early relapsed/refractory diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of lymphoma, accounts for about 30%-40% of non-Hodgkin's lymphomas and is highly heterogeneous in terms of clinical presentation and biological behavior. About 10% of patients are resistant to first-line immunochemotherapy, and up to 30%-40% of patients will relapse after treatment. Patients with relapsed/refractory (R/R) DLBCL showed poor prognosis, with a median overall survival of only 6.3 months. Those with early relapse (relapse within 12 months since diagnosis or the end of first-line treatment, ER) or primary refractory had an even worse prognosis. So there is an unmet need for treatment in this population. Previous reports and our unpublished data showed the potential connection between angiogenesis and first-line treatment failure. Accordingly, we assume that the combination of anlotinib and RGEMOX regimen may improve the response rate of patients with early relapsed/refractory DLBCL, increasing the feasibility of follow-up ASCT, and improving long-term survival of this subgroup of patients.

A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL

Prospective, Single-center, Phase II Clinical Study of Anlotinib in Combination With Rituximab，Gemcitabine and Oxaliplatin (A-RGEMOX) in the Treatment of Early Relapsed/Refractory Diffuse Large B-cell Lymphoma

Zhejiang Cancer Hospital

Chief physician

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Participants will receive EZM0414 in continuous 28-day cycles. EZM0414 will be administered orally once daily (QD) without food.

Participants who receive EZM0414 at Maximum tolerated dose (MTD) and do not have Dose limiting toxicities (DLT) in the dose escalation part of the study will be rolled over to a cohort of this dose expansion part.

Cohort 1 for R/R MM Participants. Cohort 2 for R/R MM Participants. Cohort 3 for Participants with R/R DLBCL.

Immediate-release film-coated tablets: Six dose levels starting at 100 mg, and then 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg as well as an optional step-down dose level of 75 mg (if needed)

EZM0414

Ipsen Recruitment Enquiries

Clifton Mo, MD

Dipenkumar Modi, MD

M. Houssein Kazemi, MD

Iuliana Shapira, MD

Ruben Niesvizky, MD

Joshua Richter, MD

Moshe Y Levy, MD

Dai Chihara, MD

Mitul Gandhi, MD

Ipsen Medical Director

This study will include participants with relapsed/refractory (R/R) Multiple Myeloma (MM). MM is a type of cancer of the blood. This study will also include participants with relapsed/refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL).

DLBCL is also a type of cancer of the blood. They are referred to as 'relapsed' when the disease has come back after treatment and 'refractory' when treatment no longer works. The study has 2 main parts, called phase 1 and phase 1b. The main objective of both parts will be to evaluate the safety and tolerability of the study drug, called EZM0414.

The main objective of phase 1b will also be to determine the effectiveness of EZM0414. During phase 1 six dose levels will be tested to obtain the most tolerated dose. Participants will receive study drug at the assigned dose level every 28 days. During phase 1b participants will receive study drug at the maximum tolerated dose in 28-day cycles.

The first part of the study will be a Phase 1 dose-escalation designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of EZM0414 in subjects with R/R MM and R/R DLBCL.

Six dose levels starting at 100 mg, then 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg as well as an optional step-down dose of 75 mg (if needed) will be tested. The second part of the study is the Phase 1b dose expansion at the MTD designed to evaluate safety and efficacy in subjects with R/R DLBCL and R/R MM with or without select genetic translocation.

Dose expansion will enroll subjects in 3 cohorts: Cohort 1 for R/R MM subjects with t(4;14), Cohort 2 for R/R MM subjects without t(4;14), and Cohort 3 for subjects with R/R DLBCL.

A Study of the Safety, Tolerability and Effectiveness of EZM0414 Investigative Product in Participants With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B Cell Lymphoma

A Phase 1/1b, Open-Label, Multi-Center, Two-Part Study of SETD2 Inhibitor EZM0414 in Subjects With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B-Cell Lymphoma

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be evaluated by the Investigator based on the CTCAE, version 5.0.

Percentage of participants with clinically significant changes in vital signs will be reported. The clinical significance will be evaluated by the investigator based on the CTCAE, version 5.0.

Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be will be evaluated by the investigator based on the CTCAE, version 5.0.

Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will be evaluated by the Investigator based on the CTCAE, version 5.0.

ECOG is a 6-point performance status scale used to assess performance using participant as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 5 = dead) Performance status will be assessed per usual clinical practice and will be recorded in the medical record.

Defined as any medication or vaccine, including over-the-counter or prescription medicines, vitamins, and/or herbal supplements that the participant is receiving at the time of enrollment or received during the study.

Events will be assessed as DLTs according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0)

Recommended Phase 2 will be established by analyzing AE, clinical laboratory tests and pharmacokinetics Profile.

Defined as the proportion of responders as assessed by Investigator per International Myeloma Working Group (IMWG) 2016 guidelines for MM (Stringent complete response (sCR), Complete Response (CR), Very good partial response (VGPR), and Partial Response (PR)) or Lugano 2014 guidelines for Diffuse large B cell lymphoma (DLBCL) (CR+PR).

Defined as the time from start of treatment until the first documented PD, as assessed by Investigator per IMWG 2016 guidelines for MM or Lugano 2014 guidelines for DLBCL or death due to any cause, whichever occurs first.

Defined as the proportion of subjects who have achieved confirmed CR, sCR, PR, VGPR, minimal response or stable disease (SD) per IMWG 2016 Guidelines for MM or CR, PR, or SD per Lugano 2014 Guidelines for DLBCL since administration of EZM0414 in dose expansion part (including the cycle 1 observations of the subjects who receive EZM0414 at MTD in the dose escalation part and are rolled over to the dose expansion part).

Defined as the time from initial CR or PR to documented progression or death, whichever comes first, as assessed by Investigator per IMWG 2016 guidelines for MM or Lugano 2014 guidelines for DLBCL

Epizyme, Inc.

Anti-Inflammatory Agents

Amino Acids

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Lenalidomide

Etoposide phosphate

Ibrutinib

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

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Lenalidomide 10mg/d、15mg/d、20mg/d、25mg/d d1\~d10； 21days a cycle

Lenalidomide Oral Capsule

Huayuan Zhu, PhD& MD

Huayuan Zhu, PhD，MD

Wei Xu, PhD& MD

Previous study showed that Lenalidomide or R-GDP could achieve response in Relapse and Refractory DLBCL.The investigators therefore design this phase I study to investigate the safety and efficacy of R2-GOD in relapsed diffuse large-cell lymphoma.

Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone in Relapse and Refractory DLBCL

Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone (R2-GOD) in Treatment of Relapse/Refractory DLBCL:A Phase I Study

overall response rate after treated by R-GemOx or R-miniCHOP overall response rate after treated by R2-GOD regimen regimen

from date of inclusion to date of progression, relapse, or death from any causePFS：from date of inclusion to date of progression, relapse, or death from any cause

from the date of inclusion to date of death, irrespective of cause

The First Affiliated Hospital with Nanjing Medical University

Professor

Zanubrutinib

All patients will receive 3 cycles of ZR2-ICE immunochemotherapy every three weeks.

* Drug: zanubrutinib Oral Capsule
* Drug: lenalidomide Oral Capsule
* Drug: R-ICE chemotherapy

ZR2-ICE

Hong-Hui Huang, Professor

Honghui Huang, MD

This is a prospective, single center, single arm, open label study of zanubrutinib, lenalidomide in combination with Rituximab-ICE for treatment of relapsed/refractory diffuse large B-cell lymphoma.

Zanubrutinib+Lenalidomide+R-ICE in Relapsed/Refractory DLBCL

A Prospective, Single Arm, Open Label Study to Evaluate the Safety and Efficacy of Zanubrutinib, Lenalidomide With R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma.

To evaluate the efficacy in terms of objective response rate including CR and PR rate after three cycles of ZR2-ICE

To evaluate the efficacy in terms of Complete Response Rate after three cycles of ZR2-ICE

Among participants who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression

Progression-free survival is defined as the time from enrolment to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.

Overall survival is defined as the time from enrolment to death due to any cause.

Incidence of Treatment-Emergent Adverse Events

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL	NCT06086197	Diffuse Large B... Diffuse Large B...	Anlotinib hydro...	18 Years -	Zhejiang Cancer Hospital
A Study of the Safety, Tolerability and Effectiveness of EZM0414 Investigative Product in Participants With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B Cell Lymphoma	NCT05121103	Multiple Myelom... Diffuse Large B... Diffuse Large B... Multiple Myelom...	EZM0414	18 Years -	Ipsen
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.
Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone in Relapse and Refractory DLBCL	NCT03795571	Diffuse Large B... Diffuse Large B...	Rituximab Gemcitabine Oxaliplatin Dexamethasone Lenalidomide Or...	18 Years - 65 Years	The First Affiliated Hospital with Nanjing Medical University
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.
Zanubrutinib+Lenalidomide+R-ICE in Relapsed/Refractory DLBCL	NCT06033820	Diffuse Large B... Diffuse Large B...	ZR2-ICE	18 Years - 75 Years	RenJi Hospital
Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone in Relapse and Refractory DLBCL	NCT03795571	Diffuse Large B... Diffuse Large B...	Rituximab Gemcitabine Oxaliplatin Dexamethasone Lenalidomide Or...	18 Years - 65 Years	The First Affiliated Hospital with Nanjing Medical University
A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL	NCT06086197	Diffuse Large B... Diffuse Large B...	Anlotinib hydro...	18 Years -	Zhejiang Cancer Hospital
A Study of the Safety, Tolerability and Effectiveness of EZM0414 Investigative Product in Participants With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B Cell Lymphoma	NCT05121103	Multiple Myelom... Diffuse Large B... Diffuse Large B... Multiple Myelom...	EZM0414	18 Years -	Ipsen

Spots Global Cancer Trial Database for diffuse large b cell lymphoma refractory