Condition category
Cancer
Date applied
21/03/2019
Date assigned
27/03/2019
Last edited
27/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Matching the right drug with the right patient at the right time is a challenging task in cancer treatment. In cancer, most if not all precision medicine strategies investigated so far are based on molecular profiling or genomics. However, patient stratification and patient-drug matching based on these approaches has been found to be highly limited due to the still incomplete understanding of the relationship between cancer genotype and phenotype. Functional diagnostic tests measure how living tumor cells extracted from patients react after being exposed to drugs in-vitro and can support the identification of effective and personalized treatments. Unfortunately there are no standardized in-vitro diagnostic platforms to execute these tests and whose clinical utility has been demonstrated. The aim of this study is to test the performance of the Sponsor’s in-vitro diagnostic test to predict a patient’s response to anticancer drugs, where the test is executed by an automated and standardized analytical system that measures the response of live tumor cells of the patient exposed in-vitro to the drugs.

Who can participate?
Patients aged 18 and over with a confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL), Hodgkin Lymphoma (HL) or Non Hodgkin Lymphoma (NHL) requiring drug-based treatment or, in case of CLL in “watch and wait” status.

What does the study involve?
Patients follow the prescribed therapeutic indications according to regular clinical practice and do not undergo any procedure different from the standard clinical practice. Lymph node biopsies (tissue samples) from lymphoma patients are analyzed before treatment start. Fresh and frozen blood or bone marrow samples from lymphoma and Chronic Lymphocytic Leukemia (CLL) patients are nalyzed both before treatment start and during treatment. Patients do not undergo any procedures different from the standard clinical practice. Samples collected are processed to test the response of the tumor cells to treatments selected by the clinician. The treatments tested on the cells extracted from the patient samples can include the standard treatment selected by the clinician, other treatments approved for CLL or Lymphomas as well as treatments approved for other diseases. Test results are compared with the response of the patients to the treatment.

What are the possible benefits and risks of participating?
There are no benefits or risks to the patient from participating in this study because there are no invasive tests/practices and the clinical course of the patients isn’t affected. If the test works, a larger study will be performed to confirm these findings and help improving therapy personalization.

Where is the study run from?
1. AOU di Bologna, Bologna (Italy)
2. Ospedale San Raffaele, Milano (Italy)
3. Istituto Nazionale Tumori, Milano (Italy)
4. Ospedale Niguarda, Milano (Italy)

When is the study starting and how long is it expected to run for?
April 2019 to April 2023

Who is funding the study?
Cellply S.r.l., Bologna (Italy)

Who is the main contact?
Dr Pier Luigi Zinzani
pierluigi.zinzani@unibo.it

Trial website

Contact information

Type

Public

Primary contact

Miss Laura Rocchi

ORCID ID

Contact details

Via Massarenti
61
Bologna
40138
Italy
+39 (0)510397670
laura.rocchi@cellply.com

Type

Scientific

Additional contact

Prof Pier Luigi Zinzani

ORCID ID

Contact details

Institute of Hematology “L. e A. Seràgnoli”
AOU Policlinico S.Orsola-Malpighi
Via Massarenti
9
Bologna
40138
Italy
+39 (0)512144042
pierluigi.zinzani@unibo.it

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CP-CS-002

Study information

Scientific title

Evaluation of in vitro functional response profiling for precision medicine approaches: an experimental investigation of diagnostic accuracy in lymphomas and chronic lymphoproliferative syndromes

Acronym

MYLYMPH

Study hypothesis

The identification of effective treatments through precision medicine approaches based on genomics is hampered by intra-tumoral heterogeneity and by the limited understanding of the relationship between genotype and phenotype. Functional profiling based on the analysis of the in-vitro drug response of live tumor cells sampled from patients can support the identification of effective and personalized treatments. There are no standardized in-vitro diagnostic platforms to execute these tests and whose clinical utility has been demonstrated. The present study aims to evaluate the clinical impact of a standardized and automated in-vitro diagnostic platform for the execution of functional profiling tests.

Ethics approval

Approved 20/02/2019, Comitato Etico di Area Vasta Emilia Centro della regione Emilia-Romagna (CE-AVEC), Azienda Ospedaliero-Universitaria di Bologna, Policlinico s.Orsola-Malpighi via Albertoni 15-40138 Bologna, Italy, Email: cometico@aosp.bo.it, ref: 729/2018/Sper/AOUBo

Study design

Prospective multicenter experimental investigation of diagnostic accuracy with biological sample collection study

Primary study design

Observational

Secondary study design

Experimental investigation of diagnostic accuracy

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Lymphomas and chronic lymphoproliferative syndromes

Intervention

The study is focused on in-vitro studies of drug response determined by evaluating the functional response of living cells extracted from patient samples, exposed in-vitro to multiple drug-based treatments. Selected samples are characterized through molecular analysis, to correlate these results with the functional and pharmacological profile. Samples from patients in “watch and wait” status will be collected for the optimization of test parameters.

Patients will follow the prescribed therapeutic indications according to regular clinical practice and will not be subject to any procedure different from the standard clinical practice. Lymph node biopsies from lymphoma patients will be analyzed before treatment start. Fresh and frozen blood or bone marrow samples from lymphoma and Chronic Lymphocytic Leukemia patients will be analyzed both before treatment start and during treatment. Patients will not be subjected to any procedure different from the standard clinical practice. Samples collected will be processed to define the in-vitro response of each patient’s tumor cells to both the treatment selected by the clinician within the standard clinical practice (including single drug treatments or combinations) and other treatments approved for the indications considered in this study or for other indications. Test results will be correlated with results from clinical tests and clinical data used to classify the disease and the response to the therapy.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Sensitivity determined as the proportion of the responders to the treatment that are correctly identified as such by Sponsor’s test
2. Specificity determined as the proportion of the non-responders to the treatment that are correctly identified as such by Sponsor’s test
3. Positive predictive value (PPV) determined as the proportion of the responders to the treatment among all the patients defined as responders by the Sponsor’s test
4. Negative predictive value (NPV) determined as the proportion of the non-responders to the treatment among all the patients defined as non-responders by the Sponsor’s test
5. Accuracy determined as the proportion of patients (both responders and non-responders) whose outcomes correctly predicted by the test among all the patients tested
[Timepoint: each restaging event]

Secondary outcome measures

1. Objective Response Rate (ORR) in patient populations identified by the test defined as the proportion of patients with complete remission or partial remission according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007; Hallek et al., 2008). [Timepoints: each restaging event]
2. Progression-Free Survival (PFS) in patient populations identified by the test defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first [Timepoint: 1 year]
3. Duration of response in patient populations identified by the test defined as the time from start of the first documentation of objective tumor response (complete response, CR or partial response, PR) to the first documentation of objective tumor progression or to death due to CLL/lymphoma, whichever comes first. [Timepoint: every 3 months for the first 2 years post treatment]
4. Clinical response, a classification of patients according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007; Hallek et al., 2008) [Timepoints: each restaging event]

Overall trial start date

01/04/2019

Overall trial end date

08/04/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Inclusion criteria for Arm A (chronic lymphocytic leukemia):
1. Confirmed diagnosis of CLL
2. Age greater than or equal to 18 years
3. Patient treatment-naïve or relapsed/refractory after previous therapy(ies)
4. Patient in “watch and wait” status or patient requiring drug-based treatment for CLL
5. Availability of clinical data (demographic data, medical history)
6. Patients must provide written informed consent

Inclusion criteria for Arm B (lymphomas):
1. Histologically-confirmed diagnosis of Hodgkin Lymphoma (HL) or Non Hodgkin Lymphoma (NHL)
2. Age greater than or equal to 18 years
3. Patient requiring drug-based therapy for the treatment of HL or NHL
4. Patient requiring a nodal or extranodal biopsy before treatment (only patients with availability biopsy performed during normal clinical practice before treatment will be enrolled)
5. Availability of clinical data (demographic data, medical history)
6. Patients must provide written informed consent

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

500

Participant exclusion criteria

Exclusion criteria for Arm A and Arm B:
1. Current therapy with anti-neoplastic or investigational agents
2. Known human immunodeficiency virus (HIV) positivity
3. Known hepatitis B surface antigen-positivity or known or suspected active hepatitis C infection
4. Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent

Recruitment start date

08/04/2019

Recruitment end date

08/10/2020

Locations

Countries of recruitment

Italy

Trial participating centre

AOU di Bologna, Policlinico S.Orsola-Malpighi, UO di Ematologia
via Massarenti 9
Bologna
40138
Italy

Trial participating centre

Ospedale San Raffaele, Unità linfomi, Dipartimento di Onco-Ematologia
Via Olgettina, 58
Milano
20132
Italy

Trial participating centre

Istituto Nazionale Tumori, Dipartimento di Ematologia e Onco-ematologia pediatrica
via Venezian 1
Milano
20133
Italy

Trial participating centre

Ospedale Niguarda, Dipartimento di Ematologia e Oncologia
Piazza Ospedale Maggiore 3
Milano
20162
Italy

Sponsor information

Organisation

CellPly.S.r.l.

Sponsor details

Via Massarenti
61
Bologna
40138
Italy
+39 (0)510397670
info@cellply.com

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

Cellply S.r.l.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results of the study will be presented and national and international conferences. Moreover, publication of results in a high-impact peer-reviewed scientific journal is planned within one year from the completion of the study

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

08/04/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

27/03/2019: Trial's existence confirmed by Comitato Etico di Area Vasta Emilia Centro della regione Emilia-Romagna (CE-AVEC).