Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications

NCT04053439 | Recruiting

• 1 other identifier: CHIP Lymphoma
• Study Type: observational
• Target: 188
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma; Chemotherapeutic Toxicity

Keywords

Clonal Hematopoiesis of Indeterminate Significance; Chemotherapy; Lymphoma; Chemotherapy complications

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 24 weeks

• 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%

  Up to 12 months after completion of chemotherapy

Secondary Outcomes (3)

• Expansion of clonal hematopoietic stem cells

  Up to 5 years after completion of chemotherapy

• Development of therapy-related myeloid neoplasm

  Up to 5 years after completion of chemotherapy

• Overall survival

  Up to 5 years after completion of chemotherapy

Study Arms (1)

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

Interventions

Blood test for determination of CHIP OTHER

Patients will have one additional blood draw to be sent for DNA extraction and sequencing for CHIP.

Lymphoma patients >=60 receiving cytotoxic chemotherapy

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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 \[ex: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), Fludarabine, fludarabine cyclophosphamide (FC), Bendamustine, cisplatin, cytarabine, dexamethasone (DHAP), etoposide, cytarabine, cisplatin, prednisone (ESHAP), gemcitabine, cisplatin and dexamethasone (GDP), Cladribine, Cyclophosphamide, Epirubicin, Vincristine, Prednisone (CEOP), dose-adjusted Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH)\]

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• The Leukemia and Lymphoma Society: collaborator
• Queen's University: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Related Publications (5)

• Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014 Dec 25;371(26):2488-98. doi: 10.1056/NEJMoa1408617. Epub 2014 Nov 26.

  PMID: 25426837 BACKGROUND

• Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landen M, Hoglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Gronberg H, Hultman CM, McCarroll SA. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014 Dec 25;371(26):2477-87. doi: 10.1056/NEJMoa1409405. Epub 2014 Nov 26.

  PMID: 25426838 BACKGROUND

• McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H, Stephens J; Understanding Society Scientific Group; Crawley C, Craig J, Scott MA, Hodkinson C, Baxter J, Rad R, Forsyth DR, Quail MA, Zeggini E, Ouwehand W, Varela I, Vassiliou GS. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep. 2015 Mar 3;10(8):1239-45. doi: 10.1016/j.celrep.2015.02.005. Epub 2015 Feb 26.

  PMID: 25732814 BACKGROUND

• Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, McMichael JF, Schmidt HK, Yellapantula V, Miller CA, Ozenberger BA, Welch JS, Link DC, Walter MJ, Mardis ER, Dipersio JF, Chen F, Wilson RK, Ley TJ, Ding L. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014 Dec;20(12):1472-8. doi: 10.1038/nm.3733. Epub 2014 Oct 19.

  PMID: 25326804 BACKGROUND

• Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015 Jul 2;126(1):9-16. doi: 10.1182/blood-2015-03-631747. Epub 2015 Apr 30.

  PMID: 25931582 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

A peripheral blood ethylenediaminetetraacetic acid (EDTA) tube will be used to obtain blood for DNA extraction.

MeSH Terms

Conditions

Lymphoma

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prasha Sasitharakumar, MHSc

CONTACT

(416) 480-5000; prasha.sasitharakumar@sunnybrook.ca

Anne Parmentier

CONTACT

416 480 5000; anne.parmentier@sunnybrook.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2019
• First Posted: August 12, 2019
• Study Start: August 8, 2019
• Primary Completion: January 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)