Clinical trial · Observational
Solving Riddles Through Sequencing
Testing the Diagnostic Supremacy of Sequencing-only Approaches in Hematologic Malignancies: an Observational Trial
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Hematologic Malignancy | Hematopoietic and Lymphoid Cell Neoplasm | ALIAS | 0.90 |
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
| Rare Diseases | — | UNRESOLVED | — |
| Refractory Leukemia | Leukemia | CURATED_BROADER | 0.78 |
| Refractory Lymphoma | Lymphoma | CURATED_BROADER | 0.78 |
| Unknown Primary Tumors | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Next Generation Sequencing | Diagnostic Test | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- Unclear diagnosis via conventional methods
- description
- The study population consists of carefully chosen patients with potential hematological malignancy, for which current diagnostic methods were not sufficient to provide clear-cut diagnosis and definitive clinical guidance. SIRIUS will be conducted for a total number of 110 patients with inconclusive diagnosis by gold standard techniques for a total of up to nine months after the first enrollment.
- interventionNames
- Diagnostic Test: Next Generation Sequencing
Primary outcomes (1)
- measure
- sequencing only versus gold standard diagnosis
- timeFrame
- Time Frame of Outcome: At diagnosis for each case/patient throughout the complete duration of study for approximately 1 year.
- description
- The primary endpoint will be assessed as follows: unclear cases will be subjected to three diagnostic algorithms: 1. Inhouse at referring site by histopathological diagnosis in the context of a hematological tumor board according to current standards 2. Current gold-standard diagnostic workup as performed routinely by the MLL 3. WGS and WTS sequencing plus matching to nearest digital sibling in 5,5k cohort We will compare the accuracy for approach #3 for each patient/case by comparing the sequencing results with the therapy guiding approach in domo and Current gold-standard diagnostic workup as performed routinely by the MLL. Accuracy and overlap or discordance will be measured in percentage (%) of total cohort. Time Frame of Outcome: At diagnosis for each case/patient throughout the complete duration of study for approximately 1 year.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 99 Years
Show eligibility criteria text
Inclusion Criteria: * Patients having been investigated with a suspected hematological disorder and: * Having unclear diagnosis after internal routine diagnosis * Unusual clinical course * Unusual r/r status or non-responder * Multiple parallel hematological conditions * Difficult/rare therapy associated/secondary neoplasms * Current diagnostic workup is not satisfactory in terms of (1) accuracy (2) clinical behavior * Only samples of patients min. 18 years of age will be used * Material with a minimum of 20% tumor content in bone marrow or peripheral blood sample * Patient´s informed consent Exclusion Criteria: * Sample is not fit for state-of-the-art diagnosis, fails initial quality control. For quality insurance we will exclude samples with wrong anticoagulant sent. Samples with damage due to meteorological reasons (freeze-thaw damage or elevated temperature) will be excluded. * Samples with to scarce material jeopardizing routine gold-standard diagnosis will be excluded (tumor content \< 20 %).
References
Publications (0)
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