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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05596968
Other study ID # Microbiota-flt3AML-2022
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date October 1, 2022
Est. completion date December 31, 2024

Study information

Verified date October 2022
Source Nanfang Hospital of Southern Medical University
Contact Li Xuan, MD
Phone +86-020-62787883
Email 356135708@qq.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3-ITD positive AML patients after allo-HSCT in terms of gut microbiome.


Description:

Hematopoietic stem cell transplantation (HSCT) is used as a potentially curative therapy for patients with hematopoietic malignancies. Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. Our previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD-positive AML patients, which is associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Some studies show that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the effect of gut microbiome on sorafenib maintenance after allo-HSCT remains unknown.


Recruitment information / eligibility

Status Recruiting
Enrollment 37
Est. completion date December 31, 2024
Est. primary completion date December 31, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - FLT3-ITD Positive AML - Allo-HSCT Recipients Exclusion Criteria: - intolerance to sorafenib pretransplantation - Cardiac dysfunction (particularly congestive heart failure) - Hepatic abnormalities (bilirubin = 3 mg/dL, aminotransferase> 2 times the upper limit of normal) - Renal dysfunction (creatinine clearance rate < 30 mL/min) - Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) - Patients with any conditions not suitable for the trial (according to the investigators' decision)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sorafenib
The initial dose of sorafenib is 400 mg orally twice daily and is adjusted in case of suspected toxicity or resistance (dose range, 200-800 mg daily).

Locations

Country Name City State
China Department of Hematology,Nanfang Hospital, Southern Medical University Guangzhou Guangdong

Sponsors (1)

Lead Sponsor Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (6)

Andrews MC, Duong CPM, Gopalakrishnan V, Iebba V, Chen WS, Derosa L, Khan MAW, Cogdill AP, White MG, Wong MC, Ferrere G, Fluckiger A, Roberti MP, Opolon P, Alou MT, Yonekura S, Roh W, Spencer CN, Curbelo IF, Vence L, Reuben A, Johnson S, Arora R, Morad G, Lastrapes M, Baruch EN, Little L, Gumbs C, Cooper ZA, Prieto PA, Wani K, Lazar AJ, Tetzlaff MT, Hudgens CW, Callahan MK, Adamow M, Postow MA, Ariyan CE, Gaudreau PO, Nezi L, Raoult D, Mihalcioiu C, Elkrief A, Pezo RC, Haydu LE, Simon JM, Tawbi HA, McQuade J, Hwu P, Hwu WJ, Amaria RN, Burton EM, Woodman SE, Watowich S, Diab A, Patel SP, Glitza IC, Wong MK, Zhao L, Zhang J, Ajami NJ, Petrosino J, Jenq RR, Davies MA, Gershenwald JE, Futreal PA, Sharma P, Allison JP, Routy B, Zitvogel L, Wargo JA. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade. Nat Med. 2021 Aug;27(8):1432-1441. doi: 10.1038/s41591-021-01406-6. Epub 2021 Jul 8. — View Citation

Han L, Zhao K, Li Y, Han H, Zhou L, Ma P, Fan Z, Sun H, Jin H, Jiang Z, Liu Q, Peng J. A gut microbiota score predicting acute graft-versus-host disease following myeloablative allogeneic hematopoietic stem cell transplantation. Am J Transplant. 2020 Apr;20(4):1014-1027. doi: 10.1111/ajt.15654. Epub 2019 Dec 12. — View Citation

Peled JU, Devlin SM, Staffas A, Lumish M, Khanin R, Littmann ER, Ling L, Kosuri S, Maloy M, Slingerland JB, Ahr KF, Porosnicu Rodriguez KA, Shono Y, Slingerland AE, Docampo MD, Sung AD, Weber D, Alousi AM, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Taur Y, Pamer EG, Jenq RR, van den Brink MRM. Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation. J Clin Oncol. 2017 May 20;35(15):1650-1659. doi: 10.1200/JCO.2016.70.3348. Epub 2017 Mar 15. — View Citation

Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, Maloy M, Clurman AG, Stein-Thoeringer CK, Markey KA, Docampo MD, Burgos da Silva M, Khan N, Gessner A, Messina JA, Romero K, Lew MV, Bush A, Bohannon L, Brereton DG, Fontana E, Amoretti LA, Wright RJ, Armijo GK, Shono Y, Sanchez-Escamilla M, Castillo Flores N, Alarcon Tomas A, Lin RJ, Yáñez San Segundo L, Shah GL, Cho C, Scordo M, Politikos I, Hayasaka K, Hasegawa Y, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Jenq RR, Teshima T, Chao NJ, Holler E, Xavier JB, Pamer EG, van den Brink MRM. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 2020 Feb 27;382(9):822-834. doi: 10.1056/NEJMoa1900623. — View Citation

Sidaway P. Intestinal microbiota predict HSCT outcome. Nat Rev Clin Oncol. 2020 May;17(5):275. doi: 10.1038/s41571-020-0351-9. — View Citation

Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, Khan MAW, Zhang X, White MG, Peterson CB, Wong MC, Morad G, Rodgers T, Badger JH, Helmink BA, Andrews MC, Rodrigues RR, Morgun A, Kim YS, Roszik J, Hoffman KL, Zheng J, Zhou Y, Medik YB, Kahn LM, Johnson S, Hudgens CW, Wani K, Gaudreau PO, Harris AL, Jamal MA, Baruch EN, Perez-Guijarro E, Day CP, Merlino G, Pazdrak B, Lochmann BS, Szczepaniak-Sloane RA, Arora R, Anderson J, Zobniw CM, Posada E, Sirmans E, Simon J, Haydu LE, Burton EM, Wang L, Dang M, Clise-Dwyer K, Schneider S, Chapman T, Anang NAS, Duncan S, Toker J, Malke JC, Glitza IC, Amaria RN, Tawbi HA, Diab A, Wong MK, Patel SP, Woodman SE, Davies MA, Ross MI, Gershenwald JE, Lee JE, Hwu P, Jensen V, Samuels Y, Straussman R, Ajami NJ, Nelson KC, Nezi L, Petrosino JF, Futreal PA, Lazar AJ, Hu J, Jenq RR, Tetzlaff MT, Yan Y, Garrett WS, Huttenhower C, Sharma P, Watowich SS, Allison JP, Cohen L, Trinchieri G, Daniel CR, Wargo JA. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021 Dec 24;374(6575):1632-1640. doi: 10.1126/science.aaz7015. Epub 2021 Dec 23. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Variation of Gut Microbiota Composition and Diversity Variation of gut microbiota composition and diversity, as determined by 16s rRNA sequencing of serial stool samples, during Sorafenib Maintenance Therapy. 3 months
Secondary Variation of gut barrier integrity As determined by serum levels of zonulin, I-FABP, and citrulline or other potential candidates. 3 months
Secondary NRM Non-relapse-mortality 1 year
Secondary Acute GVHD Acute Graft-Versus-Host Disease 100 days
Secondary Chronic GVHD Chronic Graft-Versus-Host Disease 1 year
Secondary AEs Adverse Events 1 year
Secondary OS Overall Survival 1 year
Secondary LFS Leukemia-free Survival 1 year
Secondary Relapse Cumulative incidence of relapse 1 year
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