Hematologic DiseasesSMARTNCT03488641
Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer
An observational study of Hematologic Diseases and Treatment, run by German Cancer Research Center at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Diseases, Treatment
- What is being tested?
- ex-vivo drug response assay
- How many people
- 80 participants
- Where
- 1 siteGermany
- Study dates
- 16 Apr 2018to 2 Aug 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with diagnosis of a hematological malignany with the need of treatment
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer (SMARTrial)
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.
Read the 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
- Being tested
- ex-vivo drug response assay
- Keywords
- Biomarker, Signal Transduction Pathway Deregulation, Outcome, Drug sensitivity testing, Targeted Therapy, Genomic landscape
- Medical subject headings
- Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ex-vivo drug response assayDiagnostic test
drug sensitivity testing of primary patient derived cancer cells
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of completed drug sensitivity testing
Patients' sample (blood, bonemarrow aspirate, tissue of lymphnode) will collected on day 0. Ex-vivo drug sensitivity testing will be performed.
Measured: 7 days
Secondary outcomes (2)
Accuracy of patients' drug response prediction by ex-vivo drug profiling
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
Measured: from date of inclusion until date of best treatment response (latest 12 months)
Prediction of time to next treatment
prediction of time to next treatment by a mathematical model based on ex-vivo drug response testing
Measured: from date of inclusion until change of treatment (latest 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2018
- Study start16 Apr 2018
- Primary completion30 Jul 2021
- Study completion2 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- German Cancer Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Heidelberg
- Responsible party
- Principal investigator, Sascha Dietrich, German Cancer Research Center
- Investigators
- Sascha Dietrich, MD, Principal investigator, University Hospital Heidelberg and DKFZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03488641
- Sponsor's protocol ID
- SMART
- Acronym
- SMART
- Status last verified
- Nov 2021
- First submitted
- 28 Mar 2018
- Last updated
- 1 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 37783805
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer (SMARTrial)
- ClinicalTrials.gov ID
- NCT03488641
- Acronym / sponsor ID
- SMART / SMART
- Conditions
- Hematologic Diseases, Treatment
- Keywords
- Biomarker, Signal Transduction Pathway Deregulation, Outcome, Drug sensitivity testing, Targeted Therapy, Genomic landscape
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- German Cancer Research CenterUniversity, hospital or other
- Collaborators
- University Hospital Heidelberg
- Study start
- 16 Apr 2018 (actual)
- Primary completion
- 30 Jul 2021 (actual)
- Study completion
- 2 Aug 2021 (actual)
- First posted
- 5 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with diagnosis of a hematological malignany with the need of treatment
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ex-vivo drug response assaydrug sensitivity testing of primary patient derived cancer cells | Diagnostic test | – |
Primary outcome
Rate of completed drug sensitivity testing
Time frame: 7 days
Patients' sample (blood, bonemarrow aspirate, tissue of lymphnode) will collected on day 0. Ex-vivo drug sensitivity testing will be performed.
2 secondary outcomes
Accuracy of patients' drug response prediction by ex-vivo drug profiling
Time frame: from date of inclusion until date of best treatment response (latest 12 months)
Prediction of time to next treatment
Time frame: from date of inclusion until change of treatment (latest 12 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2021.
- Derived from this study: PubMed 37783805Liebers 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sascha Dietrich, MD principal investigator
University Hospital Heidelberg and DKFZ
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematologic Diseases and Treatment, run by German Cancer Research Center at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of completed drug sensitivity testing (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03488641, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2021.