Comprehensive Genomic Profiling and Next Generation Functional Drug Screening for Patients With Aggressive Haematological Malignancies

Study Overview
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Brief Summary
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EXALT-2 is a prospective, randomized, three arm study for treatment decision guided either by either comprehensive genomic profiling, next generation drug screening or physician's choice

Official Title
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Comprehensive Genomic Profiling and Next Generation Functional Drug Screening for Patients With Aggressive Haematological Malignancies: Next Generation Personal Hematology

Conditions
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Advanced Lymphoma, Refractory Lymphoma, Refractory Leukemia, Refractory Acute Myeloid Leukemia, Refractory T-Cell Lymphoma

Intervention / Treatment
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* Diagnostic Test: Next generation functional drug screening
* Diagnostic Test: Comprehensive genomic profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient is suffering from aggressive haematological disease AND has undergone at least two lines of previous therapies AND/OR has undergone at least one previous therapy and no standard treatment is available in the specific disease setting and disease specific guidelines recommend treatment in studies. duration of last response is less than 6 months defined as first day of last treatment to date of relapse, the response duration has to be available with dates (dd/mm/yyyy) for initiation of and relapse to previous treatment. best response to previous treatment has to be available. The patient is able to give written informed consent and wishes to undergo further therapy further therapy is medically feasible tumor cell-containing samples can be obtained Exclusion Criteria: current participation in another experimental clinical trial performance status does not allow participation (ECOG ˃ 1) pregnancy, tested at screening patient suffers from classical or nodular, lymphocyte predominant Hodgkins lymphoma. other malignoma, diagnosed <1a before inclusion (except localized squamous cell carcinoma of the skin, surgically curable melanoma of the skin, basal cell carcinoma of the skin)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Next generation functional drug screening<br> | Diagnostic Test: Next generation functional drug screening<br>* High-throughput image based in-vitro drug screening on primary patient tumor cells<br>Diagnostic Test: Comprehensive genomic profiling<br>* Comprehensive targeted profiling of genetic aberrations on primary patient tumor material<br>* Other names: FoundationOne Heme;|
| Comprehensive genomic profiling<br> | Diagnostic Test: Next generation functional drug screening<br>* High-throughput image based in-vitro drug screening on primary patient tumor cells<br>Diagnostic Test: Comprehensive genomic profiling<br>* Comprehensive targeted profiling of genetic aberrations on primary patient tumor material<br>* Other names: FoundationOne Heme;|
| Physician's choice<br> | Diagnostic Test: Next generation functional drug screening<br>* High-throughput image based in-vitro drug screening on primary patient tumor cells<br>Diagnostic Test: Comprehensive genomic profiling<br>* Comprehensive targeted profiling of genetic aberrations on primary patient tumor material<br>* Other names: FoundationOne Heme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a ratio ≥1.3 of progression free survival (PFS) compared to most recent treatment | The study aims to identify if next-generation functional drug screening (ngFDS) and/or comprehensive genomic profiling (CGP; FoundationOne®Heme) compared to physicians' choice guided treatment will have an increased percentage of patients with a ratio ≥1.3 of progression free survival (PFS)/PFS of most recent treatment in patients with aggressive haematological malignancies | Through study completion, an average of 8 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Ratio of PFS/PFS of most prior treatment | Average Ratio of PFS/PFS of most prior treatment | Through study completion, an average of 8 months | 
| Overall response rate (ORR) | Overall response rate (ORR) | Through study completion, an average of 8 months | 
| Number of treatable targets identified | Number of treatable targets identified | Through study completion, an average of 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Personalized medicine