Clinical trial NCT03488641: Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer
Official title: Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer (SMARTrial)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematologic Diseases
Treatment
Keywords: Biomarker
Signal Transduction Pathway Deregulation
Outcome
Drug sensitivity testing
Targeted Therapy
Genomic landscape
Lead sponsor: German Cancer Research Center
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
First posted: 2018-04-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with diagnosis of a hematological malignany with the need of treatment

Brief summary: This observational study evaluates if drug response testing can be performed within 7 days and analyzes the value of ex-vivo drug screening for hematological malignancies as a biomarker to predict outcome, clinical course and response to treatment.

Detailed description: Targeted treatments have revolutionized care of individual diseases. While a new generation of targeted drugs is emerging in leukemia and lymphoma it remains clinical reality that most genetic information is not used for therapeutic stratification. This is in part based on the shortcomings of traditional biomarker discovery within clinical trials, where throughput is limited in both, drug number and sample size. If it were possible to map the variable pathway dependencies and drug sensitivity patterns in individual patients it is likely to become an asset to identify genotype-phenotype associations, understand the underlying complexities of molecular networks and further precision medicine stratification.

To link clinical outcome and ex-vivo drug response assays, the investigators systematically measure pathway sensitivity and resistance of primary tumor cells ex-vivo using a diverse compound library for individual patients in need of treatment. By systematically analyzing ex-vivo drug response patterns, tumors should be functionally grouped, by response phenotype. While for the purpose of this study selection of a specific treatment will not be based on ex-vivo drug response assays, clinical response- and follow-up data of patients will be prospectively collected in parallel.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of a hematological malignancy: patients with leukemia, myeloma or lymphoma (e.g. ALL, AML, CLL, T-PLL, MCL, MM) who are in need of treatment and are willing to donate sufficient tumor material for ex-vivo drug sensitivity testing.
2. The treating physician needs to indicate treatment.
3. Measurable disease burden according to criteria as mention in section 3.
4. Treatment must be scheduled and the patient must be eligible for the planed treatment as judged by the treating physician.
5. Availability of 5x10e7 cells from peripheral blood draws, bone marrow aspirations or lymph node biopsies.
6. Patient's written informed consent present.
7. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

Exclusion Criteria:

1. Any condition, which precludes initiation of treatment (e.g. breast feeding, pregnancy, infections, etc.) as judged by the treating physician.
2. Any coexisting medical or psychological condition that would preclude participation in the required study procedures, as judged by the treating physician.
3. No systemic cancer treatment except for cytoreductive pretreatment within 1 week of enrollment.

Primary outcomes:
measure: Rate of completed drug sensitivity testing
timeFrame: 7 days
Secondary outcomes:
measure: Accuracy of patients' drug response prediction by ex-vivo drug profiling
timeFrame: from date of inclusion until date of best treatment response (latest 12 months)
measure: Prediction of time to next treatment
timeFrame: from date of inclusion until change of treatment (latest 12 months)
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
Study officials:
affiliation: University Hospital Heidelberg and DKFZ
name: Sascha Dietrich, MD
role: PRINCIPAL_INVESTIGATOR
References: