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

NCT ID: NCT03488641

Last Updated: 2021-12-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-04-16
• Study Completion Date: 2021-08-02

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.

Conditions

Hematologic Diseases; Treatment

Keywords

Biomarker; Signal Transduction Pathway Deregulation; Outcome; Drug sensitivity testing; Targeted Therapy; Genomic landscape

Study Design

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

Interventions

ex-vivo drug response assay

drug sensitivity testing of primary patient derived cancer cells

Intervention Type: DIAGNOSTIC_TEST

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: collaborator

German Cancer Research Center

OTHER

Sponsor Role: lead

Responsible Party

Sascha Dietrich

Sascha Dietrich, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sascha Dietrich, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg and DKFZ

Locations

University Hospital Heidelberg

Heidelberg, , Germany

Countries

Germany

References

Liebers N, Bruch PM, Terzer T, Hernandez-Hernandez M, Paramasivam N, Fitzgerald D, Altmann H, Roider T, Kolb C, Knoll M, Lenze A, Platzbecker U, Rollig C, Baldus C, Serve H, Bornhauser M, Hubschmann D, Muller-Tidow C, Stolzel F, Huber W, Benner A, Zenz T, Lu J, Dietrich S. Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial. Nat Cancer. 2023 Dec;4(12):1648-1659. doi: 10.1038/s43018-023-00645-5. Epub 2023 Oct 2.

Reference Type: DERIVED

PMID: 37783805 (View on PubMed)

Other Identifiers

SMART

Identifier Type: -

Identifier Source: org_study_id