Clinical trial NCT03992352: Composite Health Assessment Risk Model (CHARM) for Older Adults (BMT CTN 1704)
Official title: Composite Health Assessment Risk Model (CHARM) for Older Adults: Applying Pre-Transplant Comorbidity, Geriatric Assessment, and BioMarkers on Non-Relapse Mortality After Allogeneic Transplant (BMT CTN 1704)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematologic Malignancy
Lead sponsor: Center for International Blood and Marrow Transplant Research
Sponsor class: NETWORK
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Cancer Institute (NCI)
name: Blood and Marrow Transplant Clinical Trials Network
name: National Marrow Donor Program
First posted: 2019-06-20
Enrollment: 1229
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Age 60+ receiving first allogeneic Hematopoetic Cell Transplantation for a hematologic malignancy

Brief summary: Prospective observational multicenter study of allogeneic Hematopoietic Stem Cell Transplantation (HCT) in recipients 60 years and older to assess important determinants of health status to be combined into a composite health risk model to improve risk assessment of non-relapse mortality (NRM).

Detailed description: At baseline, standardized Geriatric Assessment (GA) tools incorporating subject reported data and bedside testing will be collected. HCT-Comorbidity Index (CI) scores will be assigned and C-reactive protein (CRP) and albumin will be measured locally. Serial measures at 3, 6, and 12 months for frailty, skilled facility admission, and quality of life (QOL) using PROMIS measures for physical function, depression and anxiety will be determined. Graft Versus Host Disease (GVHD) through one year, serious toxicities through day 100, cognitive status at day 100 and causes of death will be captured.

Eligibility criteria: Inclusion Criteria:

1. Subject is \> 60.0 years old at time of enrollment.
2. Hematological malignancy as an indication for allogeneic transplantation.
3. Eligible for allogeneic transplantation based on institutional standards
4. First allogeneic transplant planned. Any conditioning regimen and allogeneic donor is acceptable.
5. Able to speak and read English. Spanish, and Mandarin will be acceptable when sites have ability to perform healthcare provider tests in those languages.
6. Written informed consent

Exclusion Criteria:

1. Prior allogeneic HCT

Primary outcomes:
measure: One Year Non-Relapse Mortality
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year
measure: Cumulative Incidence of Frailty
timeFrame: 1 Year
measure: Cumulative incidence of disability
timeFrame: 1 Year
measure: Cumulative incidence of admission to a skilled nursing facility
timeFrame: 1 Year
measure: HRQOL using PROMIS domains
timeFrame: 1 Year
measure: Cumulative incidence of serious organ toxicity by day 100
timeFrame: 100 Days
measure: Cumulative incidence of acute grade 2-4 GVHD
timeFrame: 100 days
measure: Cumulative incidence of acute grade 2-4 GVHD
timeFrame: 6 months
measure: Cumulative incidence of acute grade 2-4 GVHD
timeFrame: 1 year
measure: Chronic GVHD requiring treatment with systemic immune-suppression
timeFrame: 6 months
measure: Chronic GVHD requiring treatment with systemic immune-suppression
timeFrame: 1 year
measure: Survival after development of acute grade 2-4 GVHD
timeFrame: 1 year
measure: Cognitive decline at day 100
timeFrame: Day 100
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona and Phoenix Children's Hospital
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas, Blood and Marrow Transplant Program
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital Bone Marrow Transplant Program
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medicine
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: Siedman Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Universtiy
state: Ohio
city: Oklahoma City
country: United States
facility: HCA Health Services of Oklahoma, Inc., University of OK
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health - Upstate
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospitals, Inc.
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: City of Hope Medical Center
name: Andrew Artz, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Fred Hutchinson Cancer Center
name: Mohamed Sorror, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin/CIBMTR
name: Wael Saber, MD, MS
role: STUDY_CHAIR
References:
citation: Pidala J, Craig BM, Lee SJ, Majhail N, Quinn G, Anasetti C. Practice variation in physician referral for allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2013 Jan;48(1):63-7. doi: 10.1038/bmt.2012.95. Epub 2012 Jun 18.
citation: Appelbaum FR, Anasetti C, Antin JH, Atkins H, Davies S, Devine S, Giralt S, Heslop H, Laport G, Lee SJ, Logan B, Pasquini M, Pulsipher M, Stadtmauer E, Wingard JR, Horowitz MM. Blood and marrow transplant clinical trials network state of the Science Symposium 2014. Biol Blood Marrow Transplant. 2015 Feb;21(2):202-24. doi: 10.1016/j.bbmt.2014.10.003. Epub 2014 Oct 15. No abstract available.
citation: Juliusson G, Lazarevic V, Horstedt AS, Hagberg O, Hoglund M; Swedish Acute Leukemia Registry Group. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood. 2012 Apr 26;119(17):3890-9. doi: 10.1182/blood-2011-12-379008. Epub 2012 Mar 1.
citation: Mrozek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP, Metzeler KH, Schwind S, Wu YZ, Kohlschmidt J, Pettenati MJ, Heerema NA, Block AW, Patil SR, Baer MR, Kolitz JE, Moore JO, Carroll AJ, Stone RM, Larson RA, Bloomfield CD. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012 Dec 20;30(36):4515-23. doi: 10.1200/JCO.2012.43.4738. Epub 2012 Sep 17.
citation: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. doi: 10.1038/leu.2016.225. Epub 2016 Sep 2.
citation: Rashidi A, Ebadi M, Colditz GA, DiPersio JF. Outcomes of Allogeneic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. Biol Blood Marrow Transplant. 2016 Apr;22(4):651-657. doi: 10.1016/j.bbmt.2015.10.019. Epub 2015 Oct 31.
citation: Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. doi: 10.1200/JCO.2015.62.7273. Epub 2015 Nov 2.
citation: Muffly L, Pasquini MC, Martens M, et al. Increasing Use of Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Age 70 Years and Older: A CIBMTR Study of Trends and Outcomes. Biology of Blood and Marrow Transplant.22:S68-S69.
citation: Blaise D, Furst S, Crocchiolo R, El-Cheikh J, Granata A, Harbi S, Bouabdallah R, Devillier R, Bramanti S, Lemarie C, Picard C, Chabannon C, Weiller PJ, Faucher C, Mohty B, Vey N, Castagna L. Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor. Biol Blood Marrow Transplant. 2016 Jan;22(1):119-24. doi: 10.1016/j.bbmt.2015.08.029. Epub 2015 Sep 1.
citation: Kasamon YL, Bolanos-Meade J, Prince GT, Tsai HL, McCurdy SR, Kanakry JA, Rosner GL, Brodsky RA, Perica K, Smith BD, Gladstone DE, Swinnen LJ, Showel MM, Matsui WH, Huff CA, Borrello I, Pratz KW, McDevitt MA, Gojo I, Dezern AE, Shanbhag S, Levis MJ, Luznik L, Ambinder RF, Fuchs EJ, Jones RJ. Outcomes of Nonmyeloablative HLA-Haploidentical Blood or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide in Older Adults. J Clin Oncol. 2015 Oct 1;33(28):3152-61. doi: 10.1200/JCO.2014.60.4777. Epub 2015 Aug 10.
citation: Sandhu KS, Brunstein C, DeFor T, Bejanyan N, Arora M, Warlick E, Weisdorf D, Ustun C. Umbilical Cord Blood Transplantation Outcomes in Acute Myelogenous Leukemia/Myelodysplastic Syndrome Patients Aged >/=70 Years. Biol Blood Marrow Transplant. 2016 Feb;22(2):390-393. doi: 10.1016/j.bbmt.2015.09.020. Epub 2015 Sep 28.
citation: Basak GW, Sánchez-Ortega I, Beohou E, et al. Allogeneic Hematopoietic Cell Transplantation in Elderly Patients Aged 65 and Older: A Retrospective Analysis By the Complications and Quality of Life Working Party of the EBMT. Blood. 2016;128:681-681.
citation: Soto-Perez-de-Celis E, Li D, Yuan Y, Lau YM, Hurria A. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol. 2018 Jun;19(6):e305-e316. doi: 10.1016/S1470-2045(18)30348-6. Epub 2018 Jun 1.
citation: Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8.
citation: Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. doi: 10.1182/blood-2005-05-2004. Epub 2005 Jun 30.
citation: Sorror ML, Logan BR, Zhu X, Rizzo JD, Cooke KR, McCarthy PL, Ho VT, Horowitz MM, Pasquini MC. Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index: A Center for International Blood and Marrow Transplant Research Study. Biol Blood Marrow Transplant. 2015 Aug;21(8):1479-87. doi: 10.1016/j.bbmt.2015.04.004. Epub 2015 Apr 7.
citation: Raimondi R, Tosetto A, Oneto R, Cavazzina R, Rodeghiero F, Bacigalupo A, Fanin R, Rambaldi A, Bosi A. Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index: a prospective, multicenter GITMO study. Blood. 2012 Aug 9;120(6):1327-33. doi: 10.1182/blood-2012-03-414573. Epub 2012 Jun 27.
citation: Sorror ML, Storb RF, Sandmaier BM, Maziarz RT, Pulsipher MA, Maris MB, Bhatia S, Ostronoff F, Deeg HJ, Syrjala KL, Estey E, Maloney DG, Appelbaum FR, Martin PJ, Storer BE. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol. 2014 Oct 10;32(29):3249-56. doi: 10.1200/JCO.2013.53.8157. Epub 2014 Aug 25.
citation: Muffly LS, Kocherginsky M, Stock W, Chu Q, Bishop MR, Godley LA, Kline J, Liu H, Odenike OM, Larson RA, van Besien K, Artz AS. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica. 2014 Aug;99(8):1373-9. doi: 10.3324/haematol.2014.103655. Epub 2014 May 9.
citation: Alousi AM, Le-Rademacher J, Saliba RM, Appelbaum FR, Artz A, Benjamin J, Devine SM, Kan F, Laughlin MJ, Lazarus HM, Liesveld J, Perales MA, Maziarz RT, Sabloff M, Waller EK, Eapen M, Champlin RE. Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer? Blood. 2013 Mar 28;121(13):2567-73. doi: 10.1182/blood-2012-08-453860. Epub 2013 Jan 29.
citation: Muffly LS, Boulukos M, Swanson K, Kocherginsky M, Cerro PD, Schroeder L, Pape L, Extermann M, Van Besien K, Artz AS. Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients. Biol Blood Marrow Transplant. 2013 Mar;19(3):429-34. doi: 10.1016/j.bbmt.2012.11.006. Epub 2012 Nov 15.
citation: Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017 Oct 10;17(1):230. doi: 10.1186/s12877-017-0621-2.
citation: Hurria A, Cirrincione CT, Muss HB, Kornblith AB, Barry W, Artz AS, Schmieder L, Ansari R, Tew WP, Weckstein D, Kirshner J, Togawa K, Hansen K, Katheria V, Stone R, Galinsky I, Postiglione J, Cohen HJ. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011 Apr 1;29(10):1290-6. doi: 10.1200/JCO.2010.30.6985. Epub 2011 Feb 28.
citation: Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, Feng T, Smith D, Sun CL, De Glas N, Cohen HJ, Katheria V, Doan C, Zavala L, Levi A, Akiba C, Tew WP. Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer. J Clin Oncol. 2016 Jul 10;34(20):2366-71. doi: 10.1200/JCO.2015.65.4327. Epub 2016 May 16.
citation: Holmes HM, Des Bordes JK, Kebriaei P, Yennu S, Champlin RE, Giralt S, Mohile SG. Optimal screening for geriatric assessment in older allogeneic hematopoietic cell transplantation candidates. J Geriatr Oncol. 2014 Oct 1;5(4):422-30. doi: 10.1016/j.jgo.2014.04.004. Epub 2014 May 14.
citation: Olin RL, Andreadis C, Martin TG, et al. Comprehensive Geriatric Assessment Identifies Significant Functional Impairments in Older Hematopoietic Cell Transplant Recipients. Biology of Blood and Marrow Transplant.20:S65-S66.
citation: Wood WA, Deal AM, Reeve BB, Abernethy AP, Basch E, Mitchell SA, Shatten C, Hie Kim Y, Whitley J, Serody JS, Shea T, Battaglini C. Cardiopulmonary fitness in patients undergoing hematopoietic SCT: a pilot study. Bone Marrow Transplant. 2013 Oct;48(10):1342-9. doi: 10.1038/bmt.2013.58. Epub 2013 Apr 15.
citation: Jones LW, Devlin SM, Maloy MA, Wood WA, Tuohy S, Espiritu N, Aquino J, Kendig T, Michalski MG, Gyurkocza B, Schaffer WL, Ali B, Giralt S, Jakubowski AA. Prognostic Importance of Pretransplant Functional Capacity After Allogeneic Hematopoietic Cell Transplantation. Oncologist. 2015 Nov;20(11):1290-7. doi: 10.1634/theoncologist.2015-0200. Epub 2015 Oct 7.
citation: Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.