Clinical trial NCT03878407: Identification of Patients With Age-Related Clonal Hematopoiesis (ARCH) Among Cancer Survivors
Official title: Identification of Patients With Age-Related Clonal Hematopoiesis (ARCH) Among Cancer Survivors.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cancer
Keywords: ARCH
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-03-18
Enrollment: 2400
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients over the age of 60 who had or will receive chemotherapy and/or radiation therapy for solid or hematologic malignancies at the Princess Margaret Cancer Centre

Brief summary: The purpose of this study is to see if patients with cancer have a certain amount of genetic mutations in their blood. If certain levels of mutations are found in specific genes, patients may have a condition known as ARCH. The prevalence of ARCH is higher in cancer patients who received prior chemotherapy or radiation. Studying ARCH from your blood samples may also help researchers predict which patients are more likely to be prone to heart disease. Patients who are about to start chemotherapy/radiation, and patients who have completed chemotherapy/radiation will be approached to measure the incidence of ARCH. 5-10mL blood samples will be collected before and after treatment, and if ARCH is detected in a laboratory analysis, another blood sample will be collected. Patients with ARCH will repeat the blood collection yearly, and also be referred to a cardiology clinic for follow up.

Detailed description: This is a non-randomized, single-centre, observational study assessing the incidence of ARCH in cancer survivors. Patients over the age of 60 who had or will receive chemotherapy and/or radiation therapy for solid or hematologic malignancies at the Princess Margaret Cancer Centre will be considered. Based on the time point of treatment, patients will either fall into a post or prior chemotherapy/radiation cohort. Peripheral blood will be taken and will be sequenced for ARCH DNA mutations. Patients who have ARCH-related mutations at a variable allele frequency (VAF) of at least 0.5% we will repeat the genetic sequencing yearly to assess changes in mutational spectrum and VAF over time.

Eligibility criteria: * Age ≥ 60
* Completed chemotherapy and/or radiation therapy and are being followed at Princess Margaret Cancer Centre i) Patient must be in remission for \> 3 months after completing chemotherapy or radiation ii) Predicted 5 year survival of \>75% iii) Peripheral blood counts must have returned to normal as defined by:

  1. Platelets ≥ 100 x 109/L
  2. PMN ≥ 1 x 109/L

Or

* Prior to chemotherapy and/or radiation therapy at the Princess Margaret Cancer Centre.
* All histologically/cytologically proven tumour types (solid tumours and hematologic malignancies) will be eligible.
* Received or will receive regimens of chemotherapy or radiation with doses expected to produce transient myelosuppression (PMN\<0.5x109/L) in at least 80% of treated patients (The identification and definition of appropriate myelosuppressive chemotherapy and radiation regimens will be at the discretion of the treating physician and will vary among disease sites).
* Patients must have the ability to understand the requirements of the study and provide written informed consent, which includes authorization for release of protected health information
* Patient must be willing to provide a peripheral blood sample.

Exclusion Criteria:

* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Primary outcomes:
measure: Referral to cardiology clinic
timeFrame: 6-12 months
Secondary outcomes:
measure: The incidence of ARCH stratified by tumor type.
timeFrame: 6-12 months
Other outcomes:
measure: The spectrum of mutations stratified by tumor type.
timeFrame: 6-12 months
measure: The number of patients referred to the ARCH clinic
timeFrame: 6-12 months
measure: The change in VAF over time post chemotherapy/radiation
timeFrame: 6-12 months
measure: The change in VAF pre and post chemotherapy/radiation
timeFrame: 6-12 months
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Christine Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: