Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age60+
SponsorSunnybrook Health Sciences Centre
About this trial
'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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)]
Disqualifiers
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
Trial population
Elderly patients (\>= 60 years old) being treated at a tertiary cancer centre in Toronto, ON.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Blood test for determination of CHIP
Other interventionPatients will have one additional blood draw to be sent for DNA extraction and sequencing for CHIP.
Treatment groups
188 Participants
are divided into 1 treatment groupGroup A: Lymphoma patients >=60 receiving cytotoxic chemotherapy1 intervention
Trial outcomes
Primary outcomes
1
Determine if CHIP is an independent risk factor for chemotherapy-induced complications.
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.
Time frame
Up to 24 weeks2
Emerging dysmyelopoiesis after 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%
Time frame
Up to 12 months after completion of chemotherapySecondary outcomes
1
Expansion of clonal hematopoietic stem cells
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
Time frame
Up to 5 years after completion of chemotherapy2
Development of therapy-related myeloid neoplasm
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
Time frame
Up to 5 years after completion of chemotherapy3
Overall survival
Overall survival
Time frame
Up to 5 years after completion of chemotherapySponsors and contacts
Click on the lead sponsor to view all of their trials.
Sunnybrook Health Sciences Centre
Lead sponsor
The Leukemia and Lymphoma Society
Collaborator
Queen's University
Collaborator
Source ClinicalTrials.gov