Drug Response Profiling (DRP) Registry Zurich for Hematological Malignancies

NCT ID: NCT06550102

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-01-04
• Study Completion Date: 2031-12-31

Brief Summary

This study is a prospective, non-randomized feasibility study of drug response profiling (DRP) in pediatric blood cancers. Primary cancer cells are isolated from patients and screened ex vivo at single-cell resolution using automated fluorescence microscopy. Drug sensitivity fingerprints are integrated with genetic annotations to inform the treating physician about personalized treatment options. The study aims to determine the practicability of real-time drug response profiling and its actionability in identifying patient-specific cancer dependencies in refractory disease settings.

Detailed Description

This observational study offers a platform to assess the drug sensitivity of primary leukemia cells ex vivo. The cancer cells are co-cultured in multi-well plates with supporting mesenchymal stroma cells and exposed to a library of both conventional (e.g. steroids, vincristine, asparaginase) as well as targeted chemotherapeutic agents (e.g. tyrosine kinase inhibitors, proteasome inhibitors, B-cell lymphoma 2 (BCL2) inhibitors). Cells are imaged in parallel by high-content microscopy and subsequently segmented and classified by morphology and surface antigen expression. Cell viability is quantified relative to dimethyl sulfoxide (DMSO) and as a function of drug concentration. From the measured cell counts drug-specific sensitivity parameters (e.g. half-maximal inhibitory concentration IC50, maximal inhibition Imax, area under the curve AUC) and their z-scores across the patient cohorts are calculated. Drug response profiles are correlated to clinical response after a steroid pre-phase at day 8 and multiple minimal residual disease (MRD) timepoints measured by flow cytometry (FCM) or polymerase chain reaction (PCR) as defined by the trial protocol. Data on clinical response to treatment and outcome will be enquired from the treating physician. These include the disease stage (initial diagnosis, 1st relapse, 2nd relapse) and time point of sample collection, the clinical trial and treatment arm the patient is enrolled in and/or any individualized drug treatments. Functional profiling data will be integrated with information about genetic lesions (e.g. tumor protein TP53), subtype-defining translocations such as the Philadelphia chromosome t(9;22)(q34;q11) and surface antigen expression (e.g. clusters of differentiation CD7/19/22/33/117). Cytogenetics and molecular profiling data are collected from the treating clinics in collaboration with the international relapsed acute lymphoblastic leukemia (IntReALL) study group and the international Berlin-Frankfurt-Münster (IBFM) network.

Conditions

Hematological Malignancies

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Hematological malignancy

Patients witha diagnosis of hematological malignancy (primary, relapsed or refractory) including leukemia, myeloma or lymphoma

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Pediatric and adult patients below the age of 40 years
• Diagnosis of hematological malignancy (primary, relapsed or refractory) including leukemia, myeloma or lymphoma
• Tumor material collected as part of routine diagnostics and willingness to donate tumor material for translational research
• Patient and/or guardian has signed the informed consent of the DRP registry or of a clinical trial which includes DRP as add-on research.

Exclusion Criteria

• Missing informed consent for the registry or of a clinical trial which includes DRP as add-on research

• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Children's Hospital, Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Pierre Bourquin, MD, PhD

Role: STUDY_CHAIR

University Children's Hospital Zurich

Locations

University Children's Hospital Zurich

Zurich, Canton of Zurich, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Jean-Pierre Bourquin, MD, PhD

Role: CONTACT

Jean-Pierre.Bourquin@kispi.uzh.ch

0041 44 2667304

Fabio Steffen, PhD

Role: CONTACT

fabio.steffen@kispi.uzh.ch

0041 44 510 74 58

Facility Contacts

Beat Bornhauser, PhD

Role: primary

Beat.Bornhauser@kispi.uzh.ch

0041 442497055

References

Frismantas V, Dobay MP, Rinaldi A, Tchinda J, Dunn SH, Kunz J, Richter-Pechanska P, Marovca B, Pail O, Jenni S, Diaz-Flores E, Chang BH, Brown TJ, Collins RH, Uhrig S, Balasubramanian GP, Bandapalli OR, Higi S, Eugster S, Voegeli P, Delorenzi M, Cario G, Loh ML, Schrappe M, Stanulla M, Kulozik AE, Muckenthaler MU, Saha V, Irving JA, Meisel R, Radimerski T, Von Stackelberg A, Eckert C, Tyner JW, Horvath P, Bornhauser BC, Bourquin JP. Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia. Blood. 2017 Mar 16;129(11):e26-e37. doi: 10.1182/blood-2016-09-738070. Epub 2017 Jan 25.

Reference Type: BACKGROUND

PMID: 28122742 (View on PubMed)

Other Identifiers

2021-02189

Identifier Type: -

Identifier Source: org_study_id