Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Treatment in both arms is for 6 cycles at 21 days/cycle.

E7777

Chean Eng Ooi

The purpose of this study is to evaluate whether treatment of E7777 in combination with CHOP has superior efficacy compared with CHOP alone in improving complete response rate (CRR) in first line treatment of subjects with Peripheral T-cell Lymphoma (PTCL).

A Phase 3 Trial of E7777 in Combination With CHOP Compared With CHOP Alone for the First-Line Treatment of Peripheral T-cell Lymphoma

* Pretreatment or pre-randomization (screening and baseline): 4 weeks.
* Treatment: 18 weeks.
* Follow up: 2 to 3 years after the end of study treatment. Treatment will stop upon disease progression, unacceptable toxicity, or death, whichever occurs first. The Investigator or subject may also stop study treatment at any time for safety or personal reasons; however subject should remain on study, if possible, for follow-up.

Eisai Inc.

Lymphoma, T-Cell, Cutaneous

Cutaneous T-cell Lymphoma

Participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) will receive 9 μg/kg/day of E7777, administered by intravenous drip infusion in 60 minutes (± 10 min) for Days 1 through 5 of each cycle in maximum of 8 cycles. Every cycle consists of 3 weeks.

The purpose of this study is to evaluate the objective response rate (ORR) of E7777 in participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

This is a multicenter, single-arm, open label, Phase 2 to evaluate efficacy, safety, pharmacokinetics and immunogenicity of E7777 in participants with relapsed or refractory PTCL and CTCL.

Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma

A Phase 2 Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma

ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) based on independent review of Efficacy and Safety Evaluation Committee. ORR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.

PFS: time between the date of administration of the first dose of the study drug and the date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurred first) based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). PD: Any new lesion or unequivocally increase of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method. Participants with no baseline assessments, treatment discontinuation without postbaseline tumor assessments, new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored.

DOR: Time between date of first documentation of CR or PR and PD or death due to any cause based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on revised response criteria for malignant lymphoma (Cheson,2007),skin lesion and peripheral blood disease by clinical end points and response criteria in mycosis fungoides and Sezary syndrome(Olsen,2011). DOR was assessed in responders who had CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites. PD: Any new lesion or unequivocally increase of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method. Participants with new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored.

TTR was defined as time between the date of administration of the first dose of the study drug and the date of first documentation PR or CR based on independent review of Efficacy and Safety Evaluation Committee. PR or CR were assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). TTR was only conducted among responders who had experienced CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.

CR rate was defined as the percentage of participants whose BOR was CR based on independent review of Efficacy and Safety Evaluation Committee. CR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease.

OS was defined as the time between the date of administration of the first dose of the study drug and the date of death due to any cause. Participants who were alive at cut-off were censored.

11 participants were included in the PK analysis, however AUC(0-inf), could not be estimated for 1 participant due to insufficient data for elimination rate constant.

11 participants were included in the PK analysis, however MRT, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

11 participants were included in the PK analysis, however t1/2, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

11 participants were included in the PK analysis, however CL, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

11 participants were included in the PK analysis, however Vz, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

11 participants were included in the PK analysis, however Vss, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

Accumulation Ratio of Cmax was calculated as RAC (Cmax) on Cycle 3 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1, and RAC (Cmax) on Cycle 5 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1.

Accumulation ratio of AUC was calculated as RAC (AUC) on Cycle 3 Day 1 divided by RAC (AUC) on Cycle 1 Day 1, and RAC (AUC) on Cycle 5 Day 1 divided by RAC (AUC) on Cycle 1 Day 1.

Eisai Co., Ltd.

Participants with relapsed or refractory PTCL received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks).

PTCL: E7777 9 mcg/kg/Day

Participants with CTCL received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks).

CTCL: E7777 9 mcg/kg/Day

Participant with extranodal NK/T-cell lymphoma received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks).

Other: E7777 9 mcg/kg/Day

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Japanese

Race/Ethnicity, Customized

The safety analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 evaluable postbaseline safety data.

Inquiry Service.

The full analysis set (FAS) was defined as a group of participants who received at least 1 dose of the study drug.

Objective Response Rate (ORR)

The FAS was defined as a group of participants who received at least 1 dose of the study drug.

Progression Free Survival (PFS)

The FAS was defined as a group of participants who received at least 1 dose of the study drug. Here "overall number of participants analyzed" signifies responded participants.

Duration of Response (DOR)

Time to Response (TTR)

CR Rate

Overall Survival (OS)

TEAEs

SAEs

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Cycle 1 Day 1

Cycle 3 Day 1

Cycle 5 Day 1

Participants with relapsed or refractory PTCL and CTCL received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks).

PTCL and CTCL Participants: E7777 9 mcg/kg/Day

The pharmacokinetic (PK) analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.

Cmax: Maximum Observed Serum Concentration for E7777

The PK analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 serum concentration data, and included participants who had been taken frequent blood sampling for non-compartment analysis. PK-evaluable population where data at specified time points was available.

Tmax: Time to Reach the Cmax for E7777

AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777

AUC(0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for E7777

Mean Residence Time (MRT) for E7777

t1/2: Terminal Elimination Phase Half-life for E7777

CL: Total Clearance for E7777

Vz: Volume of Distribution at Terminal Phase for E7777

Vss: Volume of Distribution at Steady State for E7777

PK analysis set: group of participants who received at least 1 dose of study drug with at least 1 serum concentration data, and included participants who had taken frequent blood sampling for non-compartment analysis. Overall number of participants analyzed is number of participants with evaluable data at Cycle 1 Day 1 and at Cycles 3 and 5 Day 1

Rac (Cmax): Accumulation Ratio of Cmax for E7777

Rac (AUC): Accumulation Ratio of AUC for E7777

Anti-E7777 antibody: Cycle 1 Day 1

Anti-E7777 antibody: Cycle 2 Day 1

Anti-E7777 antibody: Cycle 3 Day 1

Anti-E7777 antibody: Cycle 5 Day 1

Anti-E7777 antibody: Cycle 8 Day 1

Anti-E7777 antibody: Discontinuation/Completion

Anti-IL-2 antibody: Cycle 1 Day 1

Anti-IL-2 antibody: Cycle 2 Day 1

Anti-IL-2 antibody: Cycle 3 Day 1

Anti-IL-2 antibody: Cycle 5 Day 1

Anti-IL-2 antibody: Cycle 8 Day 1

Anti-IL-2 antibody: Discontinuation/Completion

The pharmacodynamics (PD) analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 each of evaluable pre- and post-baseline PD data. Participants who were evaluable for this measure at given time point were included for the assessment.

Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies

Cycle 2 Day 1

Cycle 8 Day 1

Discontinuation/Completion

The PD analysis set was defined as a group of participants who received at least 1 dose of the study drug with at least 1 each of evaluable pre- and post-baseline PD data. Participants who were evaluable for this measure at given time point were included for the assessment.

Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody

Participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) received E7777 9 microgram per kilogram per day (mcg/kg/day) as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length equal to \[=\] 3 weeks).

Participants with cutaneous T-cell lymphoma (CTCL) received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks).

Participant with extranodal natural killer (NK)/T-cell lymphoma received E7777 9 mcg/kg/day as intravenous infusion, once daily from Day 1 through Day 5 in each treatment cycle until discontinuation or Cycle 8 (each Cycle length = 3 weeks).

Overall Study

Lymphoma, Large B-Cell, Diffuse

Lymphoma, Follicular

Lymphoma, B-Cell

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Follicular Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Tisagenlecleucel

Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy

Single dose of E7777 (Maximum tolerated dose level identified in phase 1) given on Day -7 two days prior to the start of lymphodepleting chemotherapy

E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor.

Cancer Center Clinical Trials Office

Veronika Bachanova, MD

This is a single institution Phase I study to determine the maximum tolerated dose (MTD) of E7777 when given prior to cyclophosphamide/fludarabine (CY/Flu) lymphodepletion (LD) chemotherapy and Kymriah, a commercial tisagenlecleucel product, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are at a higher risk for failure of CAR-T therapy.

E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. This trial is designed to augment lymphodepletion prior to CAR-T cells by administration of a targeted immunotoxin against CD25-expressing T-cells. CD25 is expressed at high levels on Tregs but also on activated effector T cells. The use of the CAR-T cell product and associated apheresis and LD chemotherapy is considered standard of care (SOC).

The Phase I study consists of two components: dose finding to establish a maximum tolerated dose (MTD) of E7777 and a small extension component to provide an estimate of efficacy at the MTD.

A single dose of E7777 is given on Day -7, two days prior to the start of lymphodepleting chemotherapy. Up to 3 dose levels will be tested. The MTD is determined by using the continual reassessment method (CRM). Enrollment begins with Dose Level 1 using a cohort of two patients. Twenty one (21) days after the 2nd patient's tisagenlecleucel infusion the next cohort of 2 patients are assigned to the most appropriate strategy based on updated toxicity probabilities corresponding to the desired maximum toxicity rate of ≤ 25% as determined by the study statistician (or designee). Enrollment continues in cohorts of 2 separated by a minimum of 28 days until 20 patients are enrolled or 10 sequential patients are enrolled at the same dose level. No intra-cohort staggering is required.

Study of E7777 Prior to Kymriah for R/R DLBCL

Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion Prior to Tisagenlecleucel (Kymriah) Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Dose Limiting Toxicity (DLT) is defined as any of the following events based on CTCAE v5 from the 1st infusion of E7777 through 21 days after the administration of tisagenlecleucel (\~28 days after E7777).

* Grade 4 infusion related reaction (IRR) associated with E7777
* Grade 4 or Grade 3 capillary leak syndrome (CLS)
* Grade 3 or 4 liver function test abnormality that do not resolve to \<Grade 2 within 5 days
* Grade 3 or 4 non-hematologic toxicity event that occurs after the administration of E7777 and before lymphodepleting therapy
* Any adverse event that results in a delay of lymphodepleting therapy for more than 72 hours and attributed to E7777
* Any Grade 5 adverse event

Number of participants experiencing adverse events related to E7777 to determine safety of the E7777

Number of participants experiencing disease free survival (DFS) at 1 year

Number of participants experiencing overall survival (DFS) at 1 year

Number of participants experiencing non-relapse mortality at day 100 post E7777 infusion

Number of participants experiencing Grade 3 or 4 cytokine release syndrome (CRS) after tisagenlecleucel therapy.

Number of participants experiencing Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome after tisagenlecleucel therapy.

Masonic Cancer Center, University of Minnesota

Symptoms and General Pathology

Substance Related Disorders

Recurrence

Drug-Related Side Effects and Adverse Reactions

Denileukin diftitox

Participants with recurrent or refractory peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL) will be administered with Remitoro 9 microgram per kilogram (mcg/kg), intravenous (IV) infusion, over 1 hour once daily for 5 consecutive days followed by 16 days withdrawal period in a 21 day cycle (up to maximum of 8 cycles). The dosage will be adjusted depending on the condition of the participant. All the participants will be observed for up to 24 weeks prospectively.

Remitoro

The primary purpose of the study is to investigate the incidence of adverse drug reactions (ADRs) (ADR of special interest: capillary leak syndrome, infusion reaction, rhabdomyolysis, myelosuppression, infection, hepatic dysfunction, visual impairment/color blindness, ischemic heart disease/arrhythmia/cardiac failure, and severe skin disorders).

A Study of Remitoro in Participants With Recurrent or Refractory Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma (All Case Study)

Post-marketing Observational Study of Remitoro® Intravenous Injection 300 μg - Safety of Remitoro in Patients With Recurrent or Refractory Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma (All Case Study)

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Incidence of ADR, especially for capillary leak syndrome, infusion reaction, rhabdomyolysis, myelosuppression, infection, hepatic dysfunction, visual impairment/color blindness, ischemic heart disease/arrhythmia/cardiac failure, and severe skin disorders will be assessed. An ADR is defined as harmful and unintended responses to the normal administration/use of drugs, in which a causal relationship with the drug in question cannot be ruled.

Percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on physician assessment will be determined. PTCL is evaluated according to revised response criteria for malignant lymphoma (Cheson, 2007). CTCL is evaluated according to clinical endpoints and response criteria in mycosis fungoides and sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 3 Trial of E7777 in Combination With CHOP Compared With CHOP Alone for the First-Line Treatment of Peripheral T-cell Lymphoma	NCT01355783	Peripheral T-Ce...	E7777	-	Eisai Inc.
Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma	NCT02676778	Peripheral T-ce... Cutaneous T-cel...	E7777	20 Years -	Eisai Inc.
Study of E7777 Prior to Kymriah for R/R DLBCL	NCT04855253	DLBCL Diffuse Large B... High-grade B-ce... DLBCL Arising F...	E7777	18 Years -	Masonic Cancer Center, University of Minnesota
A Study of Remitoro in Participants With Recurrent or Refractory Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma (All Case Study)	NCT05137847	Lymphoma, T-cel... Lymphoma, T-cel...	Remitoro	-	Eisai Inc.
A Phase 3 Trial of E7777 in Combination With CHOP Compared With CHOP Alone for the First-Line Treatment of Peripheral T-cell Lymphoma	NCT01355783	Peripheral T-Ce...	E7777	-	Eisai Inc.

Spots Global Cancer Trial Database for e7777

Every month we try and update this database with for e7777 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 e7777

Every month we try and update this database with for e7777 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 e7777 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.