The Gut Microbiome and Sorafenib Maintenance Therapy in FLT3-ITD Positive AML After Allo-HSCT

NCT05596968 | Unknown DMC

• 1 other identifier: Microbiota-flt3AML-2022
• Study Type: observational
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation; Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

Hematopoietic Stem Cell Transplantation; Gut Microbiome; Sorafenib; FLT3-ITD; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Variation of gut barrier integrity

  3 months

• NRM

  1 year

• Acute GVHD

  100 days

• Chronic GVHD

  1 year

• AEs

  1 year

Study Arms (1)

sorafenib group

FLT3-ITD+ AML patients who receive sorafenib maintenance therapy after allo-HSCT. Sorafenib will be used from day 30 to 180 post-transplantation. 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).

Drug: Sorafenib

Interventions

Sorafenib DRUG

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).

Also known as: Nexavar, BAY 43-9006, BAY-673472, BAY 545-9085

sorafenib group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

FLT3-ITD Positive AML undergoing allo-HSCT

You may qualify if:

• FLT3-ITD Positive AML
• Allo-HSCT Recipients

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (6)

• Sidaway P. Intestinal microbiota predict HSCT outcome. Nat Rev Clin Oncol. 2020 May;17(5):275. doi: 10.1038/s41571-020-0351-9. No abstract available.

  PMID: 32203272 BACKGROUND

• 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.

  PMID: 34941392 BACKGROUND

• 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, Yanez 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.

  PMID: 32101664 BACKGROUND

• 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.

  PMID: 31605563 BACKGROUND

• 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.

  PMID: 34239137 BACKGROUND

• 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.

  PMID: 28296584 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Stool, bone marrow and/or peripheral blood samples will be collected on the first day of regimen therapy for allo-HSCT, then subsequently every 28 days until discharging from the hospital, whichever occurs sooner. After discharging from the hospital, specimens will continuously be collected on the day before sorafenib maintenance therapy, then subsequently every 28 days until 3 months after receiving sorafenib maintenance therapy. The samples were tagged and stored at -80°C until retrieval for DNA extraction and cytokine detection.

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Li Xuan, MD

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Xuan, MD

CONTACT

+86-020-62787883; 356135708@qq.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: October 25, 2022
• First Posted: October 27, 2022
• Study Start: October 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: October 27, 2022

Record last verified: 2022-10

Locations

CN (1)