UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000029982
Receipt number	R000034244
Scientific Title	A Retrospective Study of Safety and Efficacy for Re-treatment of Brentuximab-Vedotin (BV) in Patients With Relapsed/Refractory (R/R) classical Hodgkin Lymphoma (cHL)/ systemic Anaplastic Large-cell Lymphoma (sALCL)
Date of disclosure of the study information	2017/11/15
Last modified on	2019/09/02 19:15:29

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Basic information

Public title

A Retrospective Study of Safety and Efficacy for Re-treatment of Brentuximab-Vedotin (BV) in Patients With Relapsed/Refractory (R/R) classical Hodgkin Lymphoma (cHL)/ systemic Anaplastic Large-cell Lymphoma (sALCL)

Acronym

Scientific Title

Scientific Title:Acronym

Region

Japan

Condition

CD30 positive cHL or sALCL

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

Objectives

Narrative objectives1

The purpose of this study is to confirm the efficacy and safety in Japanese population who are administered with brentuximab vedotin retreatment.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Assessment

Primary outcomes

Number of Participants who Experience at least one Treatment-Emergent Adverse Events (TEAE), Overall response rate (ORR)

Key secondary outcomes

Complete response rate (CR rate), Progression-free survival (PFS), Duration of response (DOR), Time to treatment failure (TTF)

Base

Study type

Observational

Study design

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Intervention

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Eligibility

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. cHL or sALCL patients with CD30 positive
2. Patients who previously experienced a CR or PR with first brentuximab vedotin treatment and subsequently experienced disease progression or relapse were administered brentuximab vedotin retreatment*.
*Definition of brentuximab vedotin retreatment
1) Discontinued treatment of brentuximab vedotin as prior therapy after experienced a CR or PR.
2) At least single dose of brentuximab vedotin was administered after discontinued treatment of brentuximab vedotin and subsequently experienced disease progression or relapse.
3) Treatment of brentuximab vedotin after 6 weeks or more passed from the date of final dose of prior treatment of brentuximab vedotin.
4) Not the treatment of brentuximab vedotin as consolidation after SCT.
5) Monotherapy of retreatment of brentuximab vedotin (not concomitant use with other antitumor agent)
6) Re-retreatment (in the case that retreatment of brentuximab vedotin was administered after discontinued retreatment of brentuximab vedotin described above) is handled as a set of retreatment).
3. A patient who agreed with informed consent prior to the study enrollment.

Key exclusion criteria

1. Patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study (such as patients who may be coerced to give consent)

Target sample size

Research contact person

Name of lead principal investigator

1st name Jumpei

Middle name

Last name Soeda

Organization

Takeda Pharmaceutical Company Limited

Division name

Strategic Medical Research Planning, Global Medical Affairs-Japan,

Zip code

103-8668

Address

12-10, Nihonbashi 2-chome, Chuo-ku,Tokyo 103-8668

TEL

03-3278-2111

Email

C25016@sogo-medefi.jp

Public contact

Name of contact person

1st name Takeda Study Registration Call Center

Middle name

Last name Takeda Study Registration Call Center

Organization

Takeda Pharmaceutical Company Limited

Division name

Strategic Medical Research Planning, Global Medical Affairs-Japan,

Zip code

103-8668

Address

12-10, Nihonbashi 2-chome, Chuo-ku,Tokyo 103-8668

TEL

03-3278-2111

Homepage URL

Email

C25016@sogo-medefi.jp

Sponsor or person

Institute

Takeda Pharmaceutical Company Limited

Institute

Department

Personal name

Funding Source

Organization

Takeda Pharmaceutical Company Limited

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Other related organizations

Co-sponsor

Name of secondary funder(s)

IRB Contact (For public release)

Organization

Takeda Pharmaceutical Company Limited

Address

12-10, Nihonbashi 2-chome, Chuo-ku,Tokyo 103-8668

Tel

03-3278-2111

Email

C25016@sogo-medefi.jp

Secondary IDs

YES

Study ID_1

JapicCTI-173771

Org. issuing International ID_1

Japan Pharmaceutical Information Center

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Other administrative information

Date of disclosure of the study information

2017 Year 11 Month 15 Day

Related information

URL releasing protocol

https://doi.org/10.1080/10428194.2019.1654100

Publication of results

Published

Result

URL related to results and publications

https://doi.org/10.1080/10428194.2019.1654100

Number of participants that the trial has enrolled

Results

In this study, the efficacy was confirmed of retreatment with brentuximab vedotin in patients with cHL or sALCL who had achieved PR or CR with previous brentuximab vedotin therapy in Japan. AEs in patients with brentuximab vedotin retreatment did not include unexpected AEs and were generally manageable with dose modification or interruption.

Results date posted

2019 Year 09 Month 02 Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2019 Year 08 Month 22 Day

Baseline Characteristics

The median ages of patients in safety population were 48.0 years (range, 18-86 years), including 17 males out of 28 (60.7%) and 11 females out of 28 (39.3%). The median Body Mass Index (BMI)(kg/m2)at the initiation of retreatment was 21.71 (range: 14.8-33.3).
Eighteen out of 28 (64.3%) patients were cHL and 10 out of 28 patients were sALCL. All the patients (28;100%) were CD30 positive at diagnosis for lymphoma by immunochemistry. For anaplastic lymphoma kinase (ALK) status in sALCL patients, 3 out of 10 (30.0%) were positive and 6 out of 10 (70.0%) were negative, and 1 out of 10 was unknown. For Ann Arbor stage, 5 out of 28 (17.9%) were stage I, 5 out of 28 (17.9%) were stage II, 2 out of 28 (7.1%) were stage III and 14 out of 28 (50.0%) were stage IV, and 2 out of 28 (7.1%) were unknown. For B symptom, 18 out of 28 (34.3%) were without B symptom, 9 out of 28 (32.1%) were with B symptom, and 1 out of 28 (3.6%) was unknown. For Eastern Cooperative Oncology Group (ECOG) Performance Status, 8 out of 28 (28.6%) were stage 0, 13 out of 28 (46.4%) were 1, 4 out of 28 (14.3%) were 3 and 1 out of 28 (3.6%) were unknown.
For disease status relative to most recent prior therapy, 8 out of 28 (28.6%) were refractory and 20 out of 28 (71.4%) were relapse after response.

Participant flow

A total of 28 subjects (cHL; 18, sALCL; 10) were enrolled and all subjects were included in the safety population. A total of 27 subjects (cHL; 17, sALCL; 10) with exception of one patient with cHL who was not assessed for response to treatment were included in the efficacy population.

Adverse events

TEAEs occurred in 18 of 28 (64.3%) in all patients, 11 of 18 (61.1%) in cHL and 7 of 10 (70.0%) in sALCL. Fourteen of 28 (50.0 %) patients experienced peripheral neuropathy (sensory; n=13, 46.4%, and motor; n=3, 10.7%) were most observed TEAEs. TEAEs observed in 2 out of 28 (7.1%) were neutropenia and AST increased, respectively. TEAEs observed in 1 out of 28 (3.6%) were ALT increased, upper respiratory infection, hepatic enzyme increased and fever, respectively.
For TEAE severity, grade 2 TEAEs were most observed in 12 out of 28 patients (42.9%). Thereafter, grade 1, 3 or 4 TEAEs were observed in 6 out of 28 patients (21.4%), 4 out of 28 patients (14.3%) , and 1 out of 28 patients (3.6%). Thus, grade 1 and 2 TEAEs were most observed.
TEAEs in grade 4 were neutropenia in 1 out of 28 (3.6%). TEAEs in grade 3 were peripheral motor neuropathy in 2 out of 28 (7.1%), neutropenia and ALT increased in 1 out of 28 (3.6%), respectively. Peripheral sensory neuropathy were most observed TEAEs in grade 2 (10 out of 28 (35.7%)). Other TEAEs in grade 2 were upper respiratory infection, ALT increased and AST increased (1 out of 28 (3.6%)), respectively. Peripheral neuropathy (sensory; n=3, 46.4%, and motor; n=1, 3.6%) were most observed TEAEs in grade 1 (4 out of 28 (14.3%)). Other TEAEs in grade 1 were fever and hepatic enzyme increased (1 out of 28 (3.6%)), respectively.Severe TEAEs were observed as peripheral motor neuropathy in 2 out of 28 patients (7.1%). TEAEs observed during brenzuximab retreatment did not include unexpected AEs. Additionally, TEAEs were almost recovered or resolved by with dose modification or interruption (including severe TEAEs). These results suggest that AEs during brenzuximab retreatment were manageable.

Outcome measures

The ORRs for all patients with retreatment was 59.3% (95% CI: 38.8 - 77.6). The ORRs for patients with cHL and sALCL were 52.9% (95% CI: 27.8 - 77.0), and 70.0% (95% CI: 34.8-93.3), respectively.The median DOR for all patients, cHL and sALCL was 21.5 months (95% CI:2.6 - NA), 21.5 months (95% CI:3.2 - 21.5) and not reached (95% CI:2.6 - NA) , respectively. The CR rate for all patients, cHL and sALCL was 33.3% (95% CI:16.5-54.0), 7.6% (95% CI:3.8 - 43.4) and 60.0% (95% CI:26.2 - 87.8), , respectively. The median PFS for all patients, cHL and sALCL was 6.1 months (95% CI:3.3- NA), 5.3 months (95% CI:2.6-24.3) and not reached (95% CI:2.0-NA) , respectively. The median TTF for all patients, cHL and sALCL was 5.9 months (95% CI:3.3 - 12.4), 5.3 months (95% CI:2.6-12.4) and 6.1 months (95% CI:2.0-NA) , respectively.
Based on these results, the efficacy is showed in the patients with CD30 positive cHL or sALCL, who had previously achieved complete response (CR) or partial remission (PR) with prior brentuximab vedotin treatment, when who are administered brentuximab vedotin retreatment in Japan.

Plan to share IPD

IPD sharing Plan description

Progress

Recruitment status

Completed

Date of protocol fixation

2017 Year 10 Month 17 Day

Date of IRB

2019 Year 03 Month 31 Day

Anticipated trial start date

2017 Year 12 Month 15 Day

Last follow-up date

2018 Year 06 Month 25 Day

Date of closure to data entry

2018 Year 06 Month 25 Day

Date trial data considered complete

2018 Year 08 Month 03 Day

Date analysis concluded

2018 Year 09 Month 30 Day

Other

Other related information

The purpose of this study is to confirm the efficacy and safety in Japanese population who are administered with brentuximab vedotin retreatment.

Management information

Registered date

2017 Year 11 Month 15 Day

Last modified on

2019 Year 09 Month 02 Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034244

1st name	Takeda Study Registration Call Center
Middle name
Last name	Takeda Study Registration Call Center