NCT05046444: SIRIUS

Solving Riddles Through Sequencing

Recruiting now Last updated 17 December 2024

What this trial tests

trial testing Next Generation Sequencing in Leukemia in 100 participants. Currently enrolling.

Timeline

19 January 2022

Primary endpoint
31 August 2025

1 October 2026

Quick facts

Lead sponsor	Munich Leukemia Laboratory
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	100
Start date	19 January 2022
Primary completion	31 August 2025
Estimated completion	1 October 2026
Sites	1 location across Germany

Drugs / interventions tested

• Next Generation Sequencing

Conditions studied

• Leukemia — all drugs for Leukemia →
• Hematologic Malignancy — all drugs for Hematologic Malignancy →
• Rare Diseases — all drugs for Rare Diseases →
• Refractory Leukemia — all drugs for Refractory Leukemia →

Sponsor

Munich Leukemia Laboratory

Who can join

Adults 18 to 99, any sex, with Leukemia or Hematologic Malignancy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

During the last decades hematologists have excelled at improving and refining the classification, diagnosis, and thus ultimately the therapeutic decision-making process for their patients. This continuous evolution proceeded in parallel to seminal discoveries in basic science such as FISH, PCR and NGS. So far, the current WHO classification serves as reference to diagnostic decision making and is largely based on 5 diagnostic pillars: cytomorphology of peripheral blood and/or bone marrow smears, histology and immunohistochemistry of bone marrow trephine biopsies or lymph nodes, immunophenotyping, chromosome banding analysis supplemented by FISH analysis, molecular genetics including PCR and targeted panel sequencing via NGS. This leads to a swift diagnosis in 90 % of all cases. The leftover 10 % remain a challenge for hematopathologists and clinicians alike and are resolved through interdisciplinary teams in the context of specialized boards. With the advent of high throughput sequencing (mainly WGS and WTS) the possibility of a comprehensive and detailed portrait of the genetic alterations - specifically in challenging cases - has become a realistic alternative to classical methods. In SIRIUS the investigators will prospectively challenge this hypothesis to address the question of how often a better or final diagnosis can be delivered by WGS and/or WTS and if unclear cases can be efficiently resolved.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies.
   Sakuma M, Blombery P, Meggendorfer M, Haferlach C, et al · · 2023 · cited 50× · PMID 36823397 · DOI 10.1038/s41375-023-01857-5
2. Solving Riddles Through Sequencing (SIRIUS): unlocking hematologic diagnoses by whole genome and transcriptome sequencing.
   Truger M, Meggendorfer M, Walter W, Hutter S, et al · · 2026 · cited 1× · PMID 41419605 · DOI 10.1038/s41375-025-02820-2
3. A case of familial donor-derived acute myeloid leukemia with underlying pre-leukemic mutations.
   Cappelli LV, Minotti C, Meggendorfer M, Truger M, et al · · 2024 · PMID 38721723 · DOI 10.3324/haematol.2024.285156