NCT04689750

Brief Summary

Current data on the impact of donor CHIP on long-term recipient outcome remain largely speculative. Data on the impact of donor CHIP including on allograft function, immunologic dysfunction, graft versus host disease (GVHD), disease relapse and survival across various donor populations are scarce. This is a retrospective-prospective cohort study designed to determine the association between donor gene mutations and outcome following allogeneic HSCT.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
850

participants targeted

Target at P75+ for all trials

Timeline
8mo left

Started Jan 2021

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress89%
Jan 2021Dec 2026

First Submitted

Initial submission to the registry

December 24, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 30, 2020

Completed
2 days until next milestone

Study Start

First participant enrolled

January 1, 2021

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2025

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Expected
Last Updated

October 4, 2022

Status Verified

October 1, 2022

Enrollment Period

5 years

First QC Date

December 24, 2020

Last Update Submit

October 3, 2022

Conditions

Clonal Hematopoiesis

Keywords

Donor clonal hematopoiesisAllogeneic hematopoiectic stem cell transplantationOutcome

Outcome Measures

Primary Outcomes (2)

  • Overall survival (OS) of the recipient.

    This is defined as the time (in months) from the date of allo-HSCT to death from any cause (event), latest follow-up (censor) or study termination.

    5 years

  • Progression-free survival (PFS) of the recipient.

    This is defined as the time (in months) from the date of allo-HSCT to relapse/progression (event), death, latest follow-up or study termination.

    5 years

Secondary Outcomes (4)

  • Acute and chronic GVHD

    5 years

  • Leukemia of donor origin

    5 years

  • Cardiac complications

    5 years

  • Pulmonary complications

    5 years

Study Arms (1)

Allogeneic HSCT recipients and donors

Diagnostic Test: Next generation sequencing

Interventions

Next generation sequencingDIAGNOSTIC_TEST

Genetic profile of donors will be collected at the time of PBSC or BM stem cell donation. Genetic profile of recipients will be collected at 1-month, 6-month, 12-month post-HSCT and at time of relapse or occurrence of leukaemia. Gene mutations and pathogenic gene fusion will be determined in the peripheral blood and/or marrow samples by next-generation sequencing (NGS) using a myeloid-gene panel and nanopore long-read sequencing.

Allogeneic HSCT recipients and donors

Eligibility Criteria

Age18 Years+
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

This study will involve allo-HSCT recipients and their donors at Queen Mary Hospital, Hong Kong. Information on the presence of gene mutations in donor peripheral blood or bone marrow sample; gene mutations in recipient peripheral blood or bone marrow post-allo-HSCT; and donor and recipient outcome will be collected in either prospective, partial-prospective/retrospective or retrospective manner.

You may qualify if:

  • Adult aged 18 year or above
  • Donor and recipient of allo-HSCT
  • In prospective and partial prospective/retrospective case, subjects who have provided a signed written informed consent. In retrospective case, subjects who had provided a previously signed written informed consent on:
  • voluntary provision of clinical data, and
  • voluntary provision of archived/remaining specimens for genetic analysis, and
  • authorizing storage and usage of archived/remaining specimens for any further analysis

You may not qualify if:

  • \. Autologous peripheral blood stem cells or bone marrow stem cell donors for autologous HSCT

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

Related Publications (8)

  • Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015 Jul 2;126(1):9-16. doi: 10.1182/blood-2015-03-631747. Epub 2015 Apr 30.

    PMID: 25931582BACKGROUND

  • Steensma DP, Ebert BL. Clonal hematopoiesis as a model for premalignant changes during aging. Exp Hematol. 2020 Mar;83:48-56. doi: 10.1016/j.exphem.2019.12.001. Epub 2019 Dec 12.

    PMID: 31838005BACKGROUND

  • Steensma DP. Clinical Implications of Clonal Hematopoiesis. Mayo Clin Proc. 2018 Aug;93(8):1122-1130. doi: 10.1016/j.mayocp.2018.04.002. Epub 2018 Jul 4.

    PMID: 30078412BACKGROUND

  • Steensma DP. Clinical consequences of clonal hematopoiesis of indeterminate potential. Blood Adv. 2018 Nov 27;2(22):3404-3410. doi: 10.1182/bloodadvances.2018020222.

    PMID: 30482770BACKGROUND

  • Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJ, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ; HALT Pan-Leukemia Gene Panel Consortium; Brown AM, Yousif F, Trinh QM, Stein LD, Minden MD, Wang JC, Dick JE. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014 Feb 20;506(7488):328-33. doi: 10.1038/nature13038. Epub 2014 Feb 12.

    PMID: 24522528BACKGROUND

  • Gibson CJ, Kennedy JA, Nikiforow S, Kuo FC, Alyea EP, Ho V, Ritz J, Soiffer R, Antin JH, Lindsley RC. Donor-engrafted CHIP is common among stem cell transplant recipients with unexplained cytopenias. Blood. 2017 Jul 6;130(1):91-94. doi: 10.1182/blood-2017-01-764951. Epub 2017 Apr 26.

    PMID: 28446434BACKGROUND

  • Frick M, Chan W, Arends CM, Hablesreiter R, Halik A, Heuser M, Michonneau D, Blau O, Hoyer K, Christen F, Galan-Sousa J, Noerenberg D, Wais V, Stadler M, Yoshida K, Schetelig J, Schuler E, Thol F, Clappier E, Christopeit M, Ayuk F, Bornhauser M, Blau IW, Ogawa S, Zemojtel T, Gerbitz A, Wagner EM, Spriewald BM, Schrezenmeier H, Kuchenbauer F, Kobbe G, Wiesneth M, Koldehoff M, Socie G, Kroeger N, Bullinger L, Thiede C, Damm F. Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol. 2019 Feb 10;37(5):375-385. doi: 10.1200/JCO.2018.79.2184. Epub 2018 Nov 7.

    PMID: 30403573BACKGROUND

  • Wong WH, Bhatt S, Trinkaus K, Pusic I, Elliott K, Mahajan N, Wan F, Switzer GE, Confer DL, DiPersio J, Pulsipher MA, Shah NN, Sees J, Bystry A, Blundell JR, Shaw BE, Druley TE. Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation. Sci Transl Med. 2020 Jan 15;12(526):eaax6249. doi: 10.1126/scitranslmed.aax6249.

    PMID: 31941826BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood or bone marrow

Study Officials

  • Harinder Gill, MD

    The University of Hong Kong

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Harinder Gill, MD

CONTACT

+852 22554542gillhsh@hku.hk

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 24, 2020

First Posted

December 30, 2020

Study Start

January 1, 2021

Primary Completion

December 31, 2025

Study Completion (Estimated)

December 31, 2026

Last Updated

October 4, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations

HK(1)