Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Large B-Cell, Diffuse

Lymphoproliferative Disorders

Lymphoma, B-Cell

Hematologic Diseases

Immunoproliferative Disorders

Lymphatic Diseases

Neoplasms by Histologic Type

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Dacetuzumab

Antineoplastic Agents, Immunological

1-8 mg/kg IV (in the vein) on Days 1, 4, 8, 15, 22 and 29 of Cycle 1; 8 mg/kg IV (in the vein) on Days 1, 8, 15, and 22 for Cycles 2-12.

SGN-40

Nancy Whiting, PharmD

This is a Phase II, open-label, multidose trial of SGN-40 designed to estimate objective response rate and assess toxicity in patients with relapsed DLBCL.

Study of SGN-40 in Patients With Relapsed Diffuse Large B-Cell Lymphoma

A Phase II Study of SGN-40 (Anti-huCD40 mAb) in Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)

Genentech, Inc.

Seagen Inc.

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

1-8 mg/kg IV; Days 1, 4, 8, 15, 22, 29 of Cycle 1 and Days 1, 15, 29 and 43 of Cycles 2-6.

SGN-40 (anti-huCD40 mAb)

Jonathan Drachman, MD

This is an open-label, dose-escalation study to determine the tolerability, safety profile, and antitumor activity of SGN-40 in patients with CLL. All patients will receive dose escalation during the first two weeks regardless of cohort designation.

A minimum of three patients will be entered into each dose-level cohort for five weeks. Escalation to the next cohort will occur when three patients have received at least one infusion at the highest scheduled dose level, and at least one patient has completed the entire five week dosing schedule. Cohorts will be enrolled at a maximal dose level of 3, 4, 6, or 8 mg/kg/week. Initial therapy will last for 5 weeks. Responding patients will receive additional infusions every two weeks x 4 at the maximal dose for each specific cohort.

A Safety Study in Patients With Chronic Lymphocytic Leukemia

A Phase 1/2, Multi-Dose Study of SGN-40 (Anti-huCD40 mAb) in Patients With Chronic Lymphocytic Leukemia

Jonathan Drachman, Sr. Medical Director

Hodgkin Disease

Hodgkin Lymphoma

Anti-Infective Agents

Bleomycin

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Brentuximab Vedotin

Vinblastine

Dacarbazine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine (DTIC) 375 mg/m\^2.

ABVD consists of doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine (DTIC) 375 mg/m\^2.

Brentuximab vedotin (ADCETRIS®)1.2 mg/kg by IV infusion on Days 1 and 15 of each 28-day cycle.

brentuximab vedotin

Doxorubicin: 25 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

doxorubicin

Bleomycin: 10 units/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

bleomycin

Vinblastine: 6 mg/m2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

vinblastine

Dacarbazine (DTIC): 375 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

dacarbazine

Study Director

This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin \[Adriamycin\], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin \[Adriamycin\],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)

A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma

A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

mPFS was defined as the time from the date of randomization to the date of the first of documentation of progressive disease (PD), death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for Hodgkin lymphoma (HL) after completion of frontline therapy. PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Frontline therapy is the part of standard set of treatments.

OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis were censored at the date last known to be alive.

CR rate at the end of randomized regimen per investigator was defined as the percentage of participants who achieved CR at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by IRF. CR was defined as disappearance of all evidence of disease.

EFS was defined as the time from randomization until any cause of treatment failure: PD, premature discontinuation of randomized treatment for any reason, or death due to any cause, whichever occurs first. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir per IRF.

DFS per IRF was defined as the time from CR to disease progression as determined by an IRF or to death from lymphoma or acute toxicity from treatment. CR was defined as disappearance of all evidence of disease.

ORR per IRF was defined as the percentage of participants who achieved CR or partial remission (PR) at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by an IRF. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

DOR per IRF in participants with response was the time between first documentation of response (PR or CR) and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

DOCR per IRF in participants with CR was the time between first documentation of CR and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease.

CR was defined as disappearance of all evidence of disease as determined by an IRF.

CR rate at the end of frontline therapy per IRF was defined as the percentage of participants who achieved CR at the end of frontline therapy that is after completion of either randomized regimen or alternate frontline therapy as determined by an IRF. CR was defined as disappearance of all evidence of disease.

PET negativity rate at Cycle 2 was defined as the percentage of participants with negative Cycle 2 PET results defined as Deauville score less than or equal to (\<=) 3 at Cycle 2. The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans.

The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit.

EORTC QLQ-C30 included 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/QOL scale. It has 28 questions (4-point scale where 1=not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=very poor \[worst\] to 7= excellent \[best\]). Raw scores were converted into scale scores from 0 to 100. For functional scales and global health status/QOL scale, higher scores show better QOL; for symptom scales, lower scores show better QOL. mPFS was time from date of randomization to date of first of documentation of PD, death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for HL after completion of frontline therapy. PD is any new lesion or increase by \>=50% of previously involved sites from nadir.

Takeda

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. The safety population included all enrolled participants who received at least 1 dose of any study drug.

Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.

A+AVD

Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.

ABVD

Total

The ITT population included all participants randomized to treatment.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The intent-to-treat (ITT) population included all participants randomized to treatment.

Medical Director

Hazard ratio (A+AVD/ABVD) and 95% confidence interval (CI) are based on a stratified Cox's proportional hazard regression model with stratification factors region and number of International Prognostic Factor Project (IPFP) risk factors at baseline with treatment as the explanatory variable in the model. Hazard ratio less than (\<) 1 favors A+AVD arm.

Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)

Hazard ratio (A+AVD/ABVD) and 95% CI are based on a stratified Cox's proportional hazard regression model with stratification factors region and number of IPFP risk factors at baseline with treatment as the explanatory variable in the model. Hazard ratio \<1 favors A+AVD arm.

Overall Survival (OS)

Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF

TEAE

The safety population included all enrolled participants who received at least 1 dose of any study drug.

Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

Number of Participants With Abnormal Clinical Laboratory Values

Event-free Survival (EFS) Per IRF

The ITT included all participants randomized to treatment. The ITT population where participants achieved CR.

Disease-free Survival (DFS) Per IRF

Overall Response Rate (ORR) Per IRF

The ITT population included all participants randomized to treatment. The ITT population where participants achieved confirmed response of CR or PR.

Duration of Response (DOR) Per IRF

The ITT population included all participants randomized to treatment. The ITT population where participants achieved CR.

Duration of Complete Remission (DOCR) Per IRF

Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy

Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy

Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2

Cycle 1 Day 1: ADC

Cycle 3 Day 1: ADC

Cycle 1 Day 1: TAb

Cycle 3 Day 1: TAb

The pharmacokinetic (PK) population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The intensive PK (iPK) population was the subset of PK population. The iPK population where data at specified timepoints was available.

A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)

Cycle 1 Day 1

Cycle 3 Day 1

The PK population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The iPK population was the subset of PK population. The iPK population where data at specified timepoints was available.

A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)

A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb

A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE

ATA positive

nATA positive

The safety population included all enrolled participants who received at least 1 dose of any study drug. The safety population-immunogenicity-evaluable participants where baseline and at least one postbaseline sample was available.

A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin

Baseline: With mPFS event

Without mPFS event

Change at end of treatment: with mPFS event

Change at end of treatment: without mPFS event

Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT

Overall Study

Antirheumatic Agents

Carboplatin

Etoposide

Rituximab

Ifosfamide

Etoposide phosphate

Isophosphamide mustard

SGN-40, rituximab, etoposide, carboplatin, ifosfamide

placebo, rituximab, etoposide, carboplatin, ifosfamide

2-8 mg/kg IV. Cycle 1: Days -1, 3, 8, 15; Cycles 2, 3: Days 1, 8, 15.

Volume as equivalent to corresponding SGN 40 dose IV. Cycle 1: Days -1, 3, 8, 15. Cycles 2, 3: Days 1, 8, 15.

placebo

375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1

rituximab

100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3.

etoposide

carboplatin

5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2.

ifosfamide

This is a randomized trial to estimate the activity of R-ICE plus SGN-40 vs. R-ICE plus placebo in patients with DLBCL. The study will assess safety and tolerability and will measure any additional clinical benefit observed in patients receiving SGN-40.

A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL

A Randomized Phase IIb Placebo-controlled Study of R-ICE Chemotherapy With and Without SGN-40 (Anti-CD40 Humanized Monoclonal Antibody) for Second-line Treatment of Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of SGN-40 in Patients With Relapsed Diffuse Large B-Cell Lymphoma	NCT00435916	Lymphoma, Large... Lymphoma, Non-H...	SGN-40	18 Years -	Seagen Inc.
A Safety Study in Patients With Chronic Lymphocytic Leukemia	NCT00283101	Leukemia, Lymph...	SGN-40 (anti-hu...	18 Years -	Seagen Inc.
A Safety Study in Patients With Chronic Lymphocytic Leukemia	NCT00283101	Leukemia, Lymph...	SGN-40 (anti-hu...	18 Years -	Seagen Inc.
A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma	NCT01712490	Hodgkin Lymphom...	brentuximab ved... doxorubicin bleomycin vinblastine dacarbazine	18 Years -	Takeda
A Safety Study in Patients With Chronic Lymphocytic Leukemia	NCT00283101	Leukemia, Lymph...	SGN-40 (anti-hu...	18 Years -	Seagen Inc.
A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma	NCT01712490	Hodgkin Lymphom...	brentuximab ved... doxorubicin bleomycin vinblastine dacarbazine	18 Years -	Takeda
Study of SGN-40 in Patients With Relapsed Diffuse Large B-Cell Lymphoma	NCT00435916	Lymphoma, Large... Lymphoma, Non-H...	SGN-40	18 Years -	Seagen Inc.
A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL	NCT00529503	Lymphoma, Large... Lymphoma, Non-H...	SGN-40 placebo rituximab etoposide carboplatin ifosfamide	18 Years - 75 Years	Seagen Inc.
A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL	NCT00529503	Lymphoma, Large... Lymphoma, Non-H...	SGN-40 placebo rituximab etoposide carboplatin ifosfamide	18 Years - 75 Years	Seagen Inc.

Spots Global Cancer Trial Database for antibody, monoclonal