Clinical trial NCT04053439: Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lymphoma
Chemotherapeutic Toxicity
Keywords: Clonal Hematopoiesis of Indeterminate Significance
Chemotherapy
Lymphoma
Chemotherapy complications
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: The Leukemia and Lymphoma Society
name: Queen's University
First posted: 2019-08-12
Enrollment: 188
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Elderly patients (\>= 60 years old) being treated at a tertiary cancer centre in Toronto, ON.

Brief summary: '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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine if CHIP is an independent risk factor for chemotherapy-induced complications.
timeFrame: Up to 24 weeks
measure: Emerging dysmyelopoiesis after chemotherapy
timeFrame: Up to 12 months after completion of chemotherapy
Secondary outcomes:
measure: Expansion of clonal hematopoietic stem cells
timeFrame: Up to 5 years after completion of chemotherapy
measure: Development of therapy-related myeloid neoplasm
timeFrame: Up to 5 years after completion of chemotherapy
measure: Overall survival
timeFrame: Up to 5 years after completion of chemotherapy
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Rena Buckstein, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Hubert Tsui, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen's University
name: Michael Rauh, MD
role: PRINCIPAL_INVESTIGATOR
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