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Acute LeukemiaNCT05601895

The Gut Microbiome in FLT3- AL Undergoing Allo-HSCT With Or Without Sorafenib Maintenance

An observational study of Acute Leukemia and Allogeneic Hematopoietic Stem Cell Transplantation, run by Nanfang Hospital, Southern Medical University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3 negative acute leukemia patients after allo-HSCT in terms of gut microbiome. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Sorafenib
Type of treatment
Pill or oral medicine
How many people
60 participants
Where
1 siteChina
Study dates
1 Oct 2022to 31 Dec 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: FLT3 Negative Acute Leukemia Undergoing Allo-HSCT

Who may be able to join

  • FLT3 Negative Acute Leukemia
  • Allo-HSCT Recipients

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Li Xuan, MD contact

+86-020-62787883

356135708@qq.com

China1 site, 1 recruiting

  • Department of Hematology,Nanfang Hospital, Southern Medical University

    Guangzhou, Guangdong, 510515

    Li Xuan, 15521251270, 356135708@qq.com

    Recruiting

Other trials in China

About this study

Official title: The Gut Microbiome Changes in FMS-like Tyrosine Kinase 3 (FLT3) Negative Acute Leukemia (AL) Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) With or Without Sorafenib Maintenance Post-transplantation

This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3 negative acute leukemia patients after allo-HSCT in terms of gut microbiome.

Read the detailed description

Acute leukemia is a heterogeneous group of clonal diseases. Leukemia relapse remains the main cause of treatment failure, including the patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. The investigator's previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD positive AML patients, which was associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Recent studies have shown that sorafenib is also effective in patients with FLT3-negative acute leukemia. The investigator's previous exploratory study found that salvage therapy such as sorafenib combined with chemotherapy and donor lymphocyte infusion could significantly improve the CR rate and survival in patients with recurrent FLT3-negative acute leukemia after allo-HSC. More and more studies have shown that sorafenib and allo-HSCT have synergistic GVL effect. Some studies have demonstrated that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the exact mechanism of sorafenib enhancing the GVL effect and the influence of gut microbiome on sorafenib maintenance after allo-HSCT in FLT3 negative acute leukemia patients remain unknown.

Being tested
Sorafenib
Keywords
Hematopoietic Stem Cell Transplantation, Gut Microbiome, Sorafenib, Acute Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SorafenibDrug

    Also called Nexavar, BAY 43-9006, BAY-673472, BAY 545-9085

    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).

Study groups in NCT05601895
Study groupRoleWhat they receive
sorafenib groupFLT3- acute leukemia 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).
Receives: Drug: Sorafenib
non-sorafenib groupFLT3- acute leukemia patients who do not receive sorafenib maintenance therapy after allo-HSCT.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Variation of Gut Microbiota Composition and Diversity

    Variation of gut microbiota composition and diversity, as determined by 16sV3V4 rRNA sequencing of serial stool samples, during Sorafenib maintenance therapy and the period without Sorafenib maintenance.

    Measured: 3 months

Secondary outcomes (8)

  1. Variation of gut barrier integrity

    As determined by serum levels of zonulin, I-FABP, and citrulline or other potential candidates.

    Measured: 3 months

  2. NRM

    Non-relapse mortality

    Measured: 1 year

  3. Acute GVHD

    The cumulative incidence of overall grades II-IV and grades III-IV acute GVHD will be assessed through six months after transplantation. Acute GVHD will be assessed using the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria.

    Measured: 100 days

  4. Chronic GVHD

    The cumulative incidence of overall grades of chronic GVHD will be assessed through 1 year after transplantation according to the 2014 NIH Consensus.

    Measured: 1 year

  5. AEs

    Adverse Events

    Measured: 1 year

  6. OS

    Overall Survival

    Measured: 1 year

  7. LFS

    Leukemia-Free Survival

    Measured: 1 year

  8. Relapse

    Cumulative incidence of relapse

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2022
  2. Study start1 Oct 2022
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05601895
Sponsor's protocol ID
Microbiota-Sora-FLT3-AL-2022
Status last verified
Oct 2022
First submitted
25 Oct 2022
Last updated
1 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 32203272

  • 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.

    PubMed 34941392

  • 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.

    PubMed 32101664

  • 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.

    PubMed 31605563

  • 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.

    PubMed 34239137

  • 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.

    PubMed 28296584

Questions about this trial

What is this clinical trial studying?

An observational study of Acute Leukemia and Allogeneic Hematopoietic Stem Cell Transplantation, run by Nanfang Hospital, Southern Medical University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Li Xuan, MD (+86-020-62787883, 356135708@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Variation of Gut Microbiota Composition and Diversity (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05601895, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2022.

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