Clinical trial NCT02867891: Sorafenib In Relapse of FMS-like Tyrosine Kinase 3 (FLT3)-Internal Tandem Duplication (ITD) AML Trial
Official title: Multicenter, Observational Trial to Determine the Response Rate of Sorafenib and Donor Lymphocyte Infusions (DLI) Versus Best Available Treatment (BAT) in FLT3-ITD-mutant AML Relapse After Allogeneic Hematopoietic Cell Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Myeloid Leukemia
Keywords: FLT3-ITD
AML
allo-HSCT
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2016-08-16
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with relapse of FLT3-ITD AML after allogeneic hematopoietic stem cell transplantation

Brief summary: In this trial the investigators will evaluate the outcomes of 4 pre-defined groups of individuals according to the therapeutic intervention. The investigators will determine the outcome of each group by monitoring the survival and the response rates of patients with FLT3-ITD AML relapse after allo-HSCT.

Detailed description: The preliminary data of the investigators demonstrate potent activity of Sorafenib combined with Donor lymphocyte infusions (DLI) in relapse of FLT3-ITD+ Acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (allo-HSCT). The investigators therefore launched an observational multicenter trial. The outcomes are assessed in 4 pre-defined groups of individuals according to the therapeutic intervention (chemotherapy-alone-group, chemotherapy/DLI group, sorafenib alone group and sorafenib/DLI group). The specific interventions to the subjects of the study are assigned by the individual transplant center. The investigators will determine the outcome of each group by monitoring the survival and the response rates (complete remission, disease burden reduction, no response) of patients with FLT3-ITD AML relapse after allo-HSCT.

Eligibility criteria: Inclusion Criteria:

* Histology/PCR proven relapse of FLT3-ITD+ AML after allo-HSCT
* Age ≥18 years
* Treatment with either chemotherapy-alone, chemotherapy/DLI, sorafenib alone or sorafenib/DLI
* Written informed consent
* Ability to understand the nature of the study and the study related procedures and to comply with them

Exclusion Criteria:

* Age \< 18 years
* Lack of informed consent
* Patients that cannot be classified in one of the 4 groups: chemotherapy-alone-group, chemotherapy/DLI group, sorafenib alone group and sorafenib/DLI group

Primary outcomes:
measure: Response to treatment
timeFrame: 10 years
Secondary outcomes:
measure: Overall survival (OS) of the participants
timeFrame: 10 years
measure: Serum cytokine levels (Interleukin (IL)-15, Interferon-gamma, IL-6) of the participants.
timeFrame: 10 years
measure: Number of participants with acute graft-versus-host disease (GvHD).
timeFrame: 10 years
Other outcomes:
Locations:
Study officials:
affiliation: Medical Center University of Freiburg
name: Robert Zeiser, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Metzelder SK, Schroeder T, Finck A, Scholl S, Fey M, Gotze K, Linn YC, Kroger M, Reiter A, Salih HR, Heinicke T, Stuhlmann R, Muller L, Giagounidis A, Meyer RG, Brugger W, Vohringer M, Dreger P, Mori M, Basara N, Schafer-Eckart K, Schultheis B, Baldus C, Neubauer A, Burchert A. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia. 2012 Nov;26(11):2353-9. doi: 10.1038/leu.2012.105. Epub 2012 Apr 16.
citation: De Freitas T, Marktel S, Piemontese S, Carrabba MG, Tresoldi C, Messina C, Lupo Stanghellini MT, Assanelli A, Corti C, Bernardi M, Peccatori J, Vago L, Ciceri F. High rate of hematological responses to sorafenib in FLT3-ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation. Eur J Haematol. 2016 Jun;96(6):629-36. doi: 10.1111/ejh.12647. Epub 2015 Sep 21.