Drug Response Profiling (DRP) Registry Zurich for Hematological Malignancies (DRP_ZH)

August 12, 2024 updated by: University Children's Hospital, Zurich
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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
    • ZH
      • Zurich, ZH, Switzerland, 8032
        • Recruiting
        • University Children's Hospital Zurich
        • Contact:
        • Sub-Investigator:
          • Nastassja Scheidegger, MD
        • Sub-Investigator:
          • Fabio Steffen, PhD
        • Sub-Investigator:
          • Beat Bornhauser, PhD
        • Principal Investigator:
          • Jean-Pierre Bourquin, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Pediatric and adult patients with hematological malignancies who have undergone bone marrow aspiration, peripheral blood or lymph node biopsies as part of routine diagnostics.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of real-time ex vivo drug screening
Time Frame: 10 days
Rate of successful single-cell, image-based drug response profiling assays which are reported to the treating physician.
10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Translation to clinic
Time Frame: 10 day
Percentage of DRP assays translated into the clinic, i.e. the referring physician decides to treat the patient with one or more of the top-ranking drugs identified by DRP
10 day
In vitro sensitivity of cancer cells to drug perturbations
Time Frame: 1 month
Exploring drug sensitivity and resistance patterns by ex vivo DRP and correlations to genetic characteristics and clinical response.
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Children's Hospital, Zurich

Investigators

  • Study Chair: Jean-Pierre Bourquin, MD, PhD, University Children's Hospital Zurich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 4, 2022

Primary Completion (Estimated)

December 31, 2031

Study Completion (Estimated)

December 31, 2031

Study Registration Dates

First Submitted

August 8, 2024

First Submitted That Met QC Criteria

August 8, 2024

First Posted (Actual)

August 12, 2024

Study Record Updates

Last Update Posted (Actual)

August 15, 2024

Last Update Submitted That Met QC Criteria

August 12, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-02189

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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