UMIN-CTR Clinical Trial

Public title

Risk of hematological adverse events with the use of immune checkpoint inhibitors

Acronym

Systematic review

Scientific Title

Risk of hematological adverse events with the use of immune checkpoint inhibitors

Scientific Title:Acronym

Systematic review

Region

Japan

Condition

Solid tumors

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Immune checkpoint inhibitors (ICIs) have provided durable responses and improved patient overall survival in solid tumors. However, the true incidence and risk of hematological adverse events (AEs) are unknown. Therefore, we will conduct systematic review and meta-analysis.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The odds ratio (OR) of any grade hematological AEs will be calculated. Meta-analysis will be performed to compare the incidence of hematological AEs between ICI-containing arm and control arm.

Key secondary outcomes

The frequency of hematological AEs will be pooled using random-model meta-analysis.

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

Age-lower limit

18

years-old

<

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

We will include only English full-articles. The other article including non-English article, short article, and conference abstract will be excluded. We will include parallel-group individual randomized controlled trials (RCTs) but not cluster RCTs, or cross-over RCTs. A trial with three or more arms will be accepted. Along with superiority trials, non-inferiority trials will be allowed. Any phase RCT may be included. Trials not reporting data about safety outcomes will be excluded.
Key inclusion criteria are as follows.
(1) RCTs including ICI-containing arm and control arm in adult patients. Controls were classified as placebo or non-placebo. Non-placebo drugs were defined as any anticancer drugs.
(2) The study with multiple arms where ICI is included at least one arm.
(3) The study illustrates the outcome of hematological AEs.

Key exclusion criteria

(1) Systematic review or meta-analysis articles.
(2) Retrospective analysis.
(3) Single prospective cohort study without a control group.
(4) Non-RCT.
(5) The republished research literature is excluded unless the research includes new findings related to adverse events listed in inclusion criteria.
(6) Studies with no or insufficient safety results at the time of the literature search.
(7) Studies published in languages other than English.
Two investigators independently screened all titles, abstracts, and full texts for eligibility. Final inclusion will be decided after resolving discrepancies between the two investigators.

Target sample size

Name of lead principal investigator

1st name	Kaoru
Middle name
Last name	Minegishi

Organization

Yokohama City University Graduate School of Medicine

Division name

Department of Stem Cell and Immune Regulation

Zip code

236-0004

Address

3-9, Kanazawa, Fukuura, Yokohama

TEL

045-787-2630

Email

kaoru_t@yokohama-cu.ac.jp

Name of contact person

1st name	Kaoru
Middle name
Last name	Minegishi

Organization

Yokohama City University Graduate School of Medicine

Division name

Department of Stem Cell and Immune Regulation

Zip code

236-0004

Address

3-9, Kanazawa, Fukuura, Yokohama

TEL

045-787-2630

Homepage URL

Email

kaoru_t@yokohama-cu.ac.jp

Institute

Yokohama City University Graduate School of Medicine

Institute

Department

Personal name

Organization

Yokohama City University Graduate School of Medicine

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Yokohama City University Graduate School of Medicine

Address

3-9, Kanazawa, Fukuura, Yokohama

Tel

045-787-2630

Email

kaoru_t@yokohama-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2021

Year

11

Month

10

Day

URL releasing protocol

https://www.thejh.org/index.php/jh/article/view/1090/715

Publication of results

Published

URL related to results and publications

https://www.thejh.org/index.php/jh/article/view/1090/715

Number of participants that the trial has enrolled

20033

Results

Please refer to the following:
https://www.thejh.org/index.php/jh/article/view/1090/715

Results date posted

2023

Year

05

Month

12

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Please refer to the following:
https://www.thejh.org/index.php/jh/article/view/1090/715

Participant flow

Please refer to the following:
https://www.thejh.org/index.php/jh/article/view/1090/715

Adverse events

Please refer to the following:
https://www.thejh.org/index.php/jh/article/view/1090/715

Outcome measures

Please refer to the following:
https://www.thejh.org/index.php/jh/article/view/1090/715

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2021

Year

11

Month

10

Day

Date of IRB

2021

Year

11

Month

10

Day

Anticipated trial start date

2021

Year

11

Month

10

Day

Last follow-up date

2022

Year

03

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

We will search for candidate articles using PubMed, Cochrane, EMBASE, and Web of Science Core Collection in November 2021. A hand search will be conducted by two investigators.
RCTs meeting the following criteria will be considered for inclusion:
Participants: The patients were clinically diagnosed with any solid tumor. Tumor type is not questioned since safety profile is not largely affected by cancer type as long as the same regimen was selected.
Intervention: At least one ICI-containing arm (including ICI in monotherapy and ICI associated with other anticancer drugs) will be included. Combination ICI therapy will not be adopted. Any regimens of ICI dose will be included.
Comparison: Controls were classified as placebo or non-placebo. Non-placebo drugs were defined as any anticancer drugs.
Outcomes: Overall hematological AEs (all grade AEs and grade 3-5 AEs) of ICI therapy during the observational period will be the primary outcome of our study. Anemia, neutropenia and thrombocytopenia will be included.
Grading of AEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) system. All available events in RCTs of ICIs reported on ClinicalTrials.gov will be extracted. If reported hematological AEs are not available on ClinicalTrials.gov, events will be extracted from published RCTs. All the dichotomous primary outcomes will be compared between the two treatment arms. We will use Review Manager 5.4.

Quality assessment:
The risk of bias of each study will be assessed by Cochrane risk of bias (RoB) tool for randomized trials.

Subgroup analysis:
Subgroup analyses based on the following subgroups will be performed for the primary outcome: (i) a subgroup of trials based on tumor type, (ii) a subgroup of trials based on ICI regimen, (iii) a subgroup limited to placebo controlled trials.

Registered date

2021

Year

11

Month

10

Day

Last modified on

2023

Year

05

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000052545