SMART: Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer

Sponsor

German Cancer Research Center (Other)

Overall Status

Completed

CT.gov ID

NCT03488641

Collaborator

University Hospital Heidelberg (Other)

Enrollment

Location

39.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Diseases Treatment	Diagnostic Test: ex-vivo drug response assay

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.

Study Design

Study Type:

Observational

Actual Enrollment :

80 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer (SMARTrial)

Actual Study Start Date :

Apr 16, 2018

Actual Primary Completion Date :

Jul 30, 2021

Actual Study Completion Date :

Aug 2, 2021

Outcome Measures

Primary Outcome Measures

Rate of completed drug sensitivity testing [7 days]
Patients' sample (blood, bonemarrow aspirate, tissue of lymphnode) will collected on day 0. Ex-vivo drug sensitivity testing will be performed.

Secondary Outcome Measures

Accuracy of patients' drug response prediction by ex-vivo drug profiling [from date of inclusion until date of best treatment response (latest 12 months)]
Ex-vivo drug sensitivity categorizes drugs as sensitive/not sensitive. Results will be compared with clinical outcome of patient (response vs. stable disease as defined in the clinical response definition by protocol
Prediction of time to next treatment [from date of inclusion until change of treatment (latest 12 months)]
prediction of time to next treatment by a mathematical model based on ex-vivo drug response testing

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
The treating physician needs to indicate treatment.
Measurable disease burden according to criteria as mention in section 3.
Treatment must be scheduled and the patient must be eligible for the planed treatment as judged by the treating physician.
Availability of 5x10e7 cells from peripheral blood draws, bone marrow aspirations or lymph node biopsies.
Patient's written informed consent present.
Ability to understand the nature of the trial and the trial related procedures and to comply with them.

Exclusion Criteria:

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