Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications

July 2, 2025 updated by: Sunnybrook Health Sciences Centre

A Single Centre Cohort Study to Determine if Clonal Hematopoieses of Indeterminate Potential (CHIP) is a Risk Factor for Chemotherapy-Related Complications in Lymphoma Patients >= 60 Receiving Cytotoxic Chemotherapy

'CHIP' stands for Clonal Hematopoiesis of Indeterminate Significance, which are mutations in bone marrow stem cells that give that population of cells a survival or 'clonal' advantage for growth. This study investigates whether CHIP in lymphoma patients aged 60 years and older is a risk factor for chemotherapy-related complications like low blood counts, infections, cardiac events, hospitalizations, dose delays and dose reductions, and failure to recover normal blood counts after chemotherapy finishes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

'CHIP' stands for Clonal Hematopoiesis of Indeterminate Significance (1-4). Up to 20% of individuals in the general population acquire mutations in their bone marrow stem cells as they age that give that population of cells a survival or 'clonal' advantage for growth. The frequency of CHIP may be higher in patients with other cancers. CHIP increases with age, and has been shown to be a risk factor associated with cardiovascular disease and a tendency to the development of bone marrow cancers at a rate of 1% per year (1,2,5). CHIP is also associated with the development of bone marrow cancers that occur after chemotherapy. The investigators want to investigate whether CHIP is also a risk factor for chemotherapy-related complications like low blood counts, infections, cardiac events, hospitalizations, dose delays and dose reductions. They are also interested in determining if CHIP may explain why some patients do not recover normal blood counts after chemotherapy finishes.

The results from this study may help physicians better understand why some people have difficulty with chemotherapy (in the short and long-term) while others do not. Screening for CHIP in older patients may become a recommended standard that allows physicians to tailor anti-cancer treatment to the patient.

Study Type

Observational

Enrollment (Estimated)

188

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Elderly patients (>= 60 years old) being treated at a tertiary cancer centre in Toronto, ON.

Description

Inclusion Criteria:

  • Diagnosis of a lymphoma (ex: diffuse large B cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, Hodgkin's lymphoma, peripheral T cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic lymphoma, hairy cell leukemia, Waldenstrom's macroglobulinemia, anaplastic large cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and mantle cell lymphoma).
  • Commencing first or second-line cytotoxic chemotherapy for lymphoma with or without rituximab [ex: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), Fludarabine, fludarabine cyclophosphamide (FC), Bendamustine, cisplatin, cytarabine, dexamethasone (DHAP), etoposide, cytarabine, cisplatin, prednisone (ESHAP), gemcitabine, cisplatin and dexamethasone (GDP), Cladribine, Cyclophosphamide, Epirubicin, Vincristine, Prednisone (CEOP), dose-adjusted Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH)]

Exclusion Criteria:

  • Pre-existing diagnosis of myeloid neoplasm
  • Circulating lymphocyte count > 10 x 109/L
  • Significant uncontrolled renal or hepatic impairment [>1.5 x upper limit of normal (ULN) bilirubin, >1.5 x ULN Alanine aminotransferase (ALT), >1.5 x ULN creatinine]
  • HIV
  • Active infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Lymphoma patients >=60 receiving cytotoxic chemotherapy
Lymphoma patients >=60 receiving cytotoxic chemotherapy who have consented to DNA extraction and analysis for CHIP.
Other: Blood test for determination of CHIP
Patients will have one additional blood draw to be sent for DNA extraction and sequencing for CHIP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine if CHIP is an independent risk factor for chemotherapy-induced complications.
Time Frame: Up to 24 weeks
Complications during chemotherapy defined as any or all of the following: febrile neutropenia, new grades 3-4 anemia, thrombocytopenia and neutropenia immediately (day -1 or 0) preceding next cycle of chemotherapy, secondary dose reductions or dose delays due to myelosuppression or toxicity, cardiovascular toxicity (arrhythmias, congestive heart failure, symptomatic coronary disease), secondary granulocyte colony-stimulating factor (GCSF) use due to neutropenia, inability to complete all scheduled cycles due to chemotherapy related complications, dose delays that exceed 7 days.
Up to 24 weeks
Emerging dysmyelopoiesis after chemotherapy
Time Frame: Up to 12 months after completion of chemotherapy

The number of patients with and without CHIP who, following at 6 and 12 months post chemotherapy have:

  1. Hemoglobin, white blood cell (WBC) or platelet (PLT) count that does not recover to normal pre-chemotherapy levels
  2. Persistant macrocytosis defined as mean cell volume (MCV) > 96 fl
  3. Persistant anisocytosis defined as red cell distribution width (RDW) > 14.5%
Up to 12 months after completion of chemotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expansion of clonal hematopoietic stem cells
Time Frame: Up to 5 years after completion of chemotherapy
Expansion of clonal hematopoietic stem cells over time measured using next generation sequencing of 40 myeloid genes in patients with CHIP at baseline defined by variant allele frequency (VAF) that increases by 10% of more or the emergence of new clones
Up to 5 years after completion of chemotherapy
Development of therapy-related myeloid neoplasm
Time Frame: Up to 5 years after completion of chemotherapy
Therapy-related myeloid neoplasm defined as any of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), MDS/MPN diagnosed by bone marrow exam
Up to 5 years after completion of chemotherapy
Overall survival
Time Frame: Up to 5 years after completion of chemotherapy
Overall survival
Up to 5 years after completion of chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Queen's University
The Leukemia and Lymphoma Society

Investigators

  • Principal Investigator: Rena Buckstein, MD, FRCPC, Sunnybrook Health Sciences Centre
  • Principal Investigator: Hubert Tsui, MD, Sunnybrook Health Sciences Centre
  • Principal Investigator: Michael Rauh, MD, Queen's University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 8, 2019

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

August 8, 2019

First Submitted That Met QC Criteria

August 9, 2019

First Posted (Actual)

August 12, 2019

Study Record Updates

Last Update Posted (Actual)

July 8, 2025

Last Update Submitted That Met QC Criteria

July 2, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHIP Lymphoma

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on Blood test for determination of CHIP

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Czech Republic

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe