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Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications

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ClinicalTrials.gov Identifier: NCT04053439
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
The Leukemia and Lymphoma Society
Queen's University
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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.

Condition or disease Intervention/treatment
Lymphoma Chemotherapeutic Toxicity Other: Blood test for determination of CHIP

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.


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Study Type : Observational
Estimated Enrollment : 188 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : August 8, 2019
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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.




Primary Outcome Measures :
  1. 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.

  2. 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%


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Overall survival [ Time Frame: Up to 5 years after completion of chemotherapy ]
    Overall survival


Biospecimen Retention:   Samples With DNA
A peripheral blood ethylenediaminetetraacetic acid (EDTA) tube will be used to obtain blood for DNA extraction.


Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Elderly patients (>= 60 years old) being treated at a tertiary cancer centre in Toronto, ON.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04053439


Contacts
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Contact: Arlene Mete (416) 480-6100 ext 3835 arlene.mete@sunnybrook.ca

Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Rena Buckstein, MD    416-480-5847    rena.buckstein@sunnybrook.ca   
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
The Leukemia and Lymphoma Society
Queen's University
Investigators
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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:

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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04053439     History of Changes
Other Study ID Numbers: CHIP Lymphoma
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sunnybrook Health Sciences Centre:
Clonal Hematopoiesis of Indeterminate Significance
Chemotherapy
Lymphoma
Chemotherapy complications
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Iproplatin
Antineoplastic Agents