Early Detection and Screening of Hematological Malignancies - SANGUINE
Study Details
Study Description
Brief Summary
This is a multicenter, open-label, non-interventional controlled study to identify and characterize the epigenetic signatures for a set of hematological malignancies: Multiple myeloma (MM), pre-MM conditions [smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS)], Hodgkin lymphoma (HL), non-Hodgkin aggressive lymphoma NHL [diffuse large B cell lymphoma (DLBCL), high-grade lymphoma (HGL), follicular lymphoma (FL) and marginal zone lymphoma (MZL) transformed to large cell lymphoma], FL, MZL, de novo acute myeloid leukemia (AML), secondary AML, myelodysplastic syndrome (MDS) and healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Subjects will be screened for eligibility and then, after signing an Informed Consent Form, the first peripheral blood will be obtained.
Periodical blood samples will be obtained from the participants. Relapse patients will have their retrospective blood samples analyzed to identify early signs of disease.
The first stage (discovery phase) will include at least 30 patients from each of the following groups: MM, pre-MM conditions (SMM and MGUS), HL, aggressive NHL (DLBCL, HGL, FL, and MZL transformed to large cell lymphoma), FL, MZL, de novo AML, secondary AML, MDS, and healthy subjects.
In the second stage, at least 250 patients with MM and 250 patients with NHL, and at least 100 patients with each of the remaining blood cancer conditions mentioned above will be tested. It is expected that the majority of these patients will be tested also during the disease follow-up.
The last stage consists of the screening of a larger group of subjects with a high risk of blood cancer. This stage will include three populations: up to 1000 follow-up patients from each blood cancer: AML, lymphoma, and MM, up to 600 elderly patients (>65 years old) at risk of developing MM, and up to 400 first-degree relatives of patients (and in particular siblings). In order to allow a maximum follow-up period for at-risk subjects as part of the study, and to meet the recruitment goals, the screening, and enrollment can begin in the first stage of the trial.
In all stages, the age and sex-matched subgroups will be considered and matched.
In addition, as part of the discovery stage, bone marrow samples will be obtained at Tel-Aviv Sourasky Medical Center (TASMC) from up to 50 MM patients and up to 50 AML patients that undergo bone marrow aspiration as part of the standard care procedure. Additionally, up to 50 bone marrow samples will be taken from healthy volunteers that will undergo hip or knee replacement surgery. Blood samples will be collected from the same participants.
During the follow-up period, demographic and baseline parameters including sex, age, race, height and weight, medical history, details of initial diagnosis and treatment history, concomitant medications as well as adverse events (AEs) of special interest (see section 9.1), (serious) AEs related to study procedures, treatment for the disease and disease response will be collected (as applicable).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients with Hematological Malignancies - Discovery stage The first stage (discovery phase) will include at least 30 patients from each of the following groups: MM, pre-MM conditions (SMM and MGUS), HL, aggressive NHL (DLBCL, HGL, FL, and MZL transformed to large cell lymphoma), FL, MZL, de novo AML, secondary AML, MDS, For patients, it is expected, after signing the informed consents, that the serial samplings will be performed during the disease follow-up according to the standard clinical practice and/or recommended schedule and disease assessment plan. Bone marrow samples will be obtained at Tel-Aviv Sourasky Medical Center (TASMC) from up to 50 MM patients and up to 50 AML patients that undergo bone marrow aspiration as part of the standard care procedure. |
Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing
Classification of a broad spectrum of blood cancers based on detection of epigenetic biomarkers from genomic DNA, cell-free (cf) DNA, exosomal DNA, RNA and non-coding RNA. The identified biomarkers will include proteins, metabolites, and other characteristic biomolecules.
Year 1: During the discovery phase, all tests will be conducted by JaxBio and TAU with the aid of technical service providers. At this stage, microarray measurements will be performed on a commercial platform that will be purchased from Agilent / Illumina. All reagents needed for the test will be either purchased or produced in-house.
Years 2-3: Throughout the second phase of the project, a custom targeted microarray, HemaChip will be developed and used for all tests. The HemaChip and custom reagents will be distributed to partners' labs and all tests will be conducted at the clinical sites. Additional validation tests will be conducted by JaxBio and TAU, as needed.
Other Names:
|
| Patients with Hematological Malignancies - Second stage In the second stage, at least 250 patients with MM and 250 patients with NHL and at least 100 patients with each of the remaining blood cancer conditions mentioned above will be tested. It is expected that the majority of these patients will be tested also during the disease follow-up. For patients, it is expected, after signing the informed consents, that the serial samplings will be performed during the disease follow-up according to the standard clinical practice and/or recommended schedule and disease assessment plan |
Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing
Classification of a broad spectrum of blood cancers based on detection of epigenetic biomarkers from genomic DNA, cell-free (cf) DNA, exosomal DNA, RNA and non-coding RNA. The identified biomarkers will include proteins, metabolites, and other characteristic biomolecules.
Year 1: During the discovery phase, all tests will be conducted by JaxBio and TAU with the aid of technical service providers. At this stage, microarray measurements will be performed on a commercial platform that will be purchased from Agilent / Illumina. All reagents needed for the test will be either purchased or produced in-house.
Years 2-3: Throughout the second phase of the project, a custom targeted microarray, HemaChip will be developed and used for all tests. The HemaChip and custom reagents will be distributed to partners' labs and all tests will be conducted at the clinical sites. Additional validation tests will be conducted by JaxBio and TAU, as needed.
Other Names:
|
| Patients with Hematological Malignancies - Third stage The last stage consists in the screening of a larger group of subjects with high risk of blood cancer. This stage will include three populations: up to 1000 follow-up patients from each blood cancer: AML, lymphoma and MM. |
Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing
Classification of a broad spectrum of blood cancers based on detection of epigenetic biomarkers from genomic DNA, cell-free (cf) DNA, exosomal DNA, RNA and non-coding RNA. The identified biomarkers will include proteins, metabolites, and other characteristic biomolecules.
Year 1: During the discovery phase, all tests will be conducted by JaxBio and TAU with the aid of technical service providers. At this stage, microarray measurements will be performed on a commercial platform that will be purchased from Agilent / Illumina. All reagents needed for the test will be either purchased or produced in-house.
Years 2-3: Throughout the second phase of the project, a custom targeted microarray, HemaChip will be developed and used for all tests. The HemaChip and custom reagents will be distributed to partners' labs and all tests will be conducted at the clinical sites. Additional validation tests will be conducted by JaxBio and TAU, as needed.
Other Names:
|
| Elderly patients (>65 years old) at risk of developing MM -Third stage up to 600 elderly patients (>65 years old) at risk of developing MM In order to allow a maximum follow-up period for at-risk subjects as part of the study, and to meet the recruitment goals, the screening, and enrollment can begin in the first stage of the trial. Follow-up patients, at-risk individuals for MM, and at-risk first-degree relatives will donate blood periodically according to the follow up plan. |
Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing
Classification of a broad spectrum of blood cancers based on detection of epigenetic biomarkers from genomic DNA, cell-free (cf) DNA, exosomal DNA, RNA and non-coding RNA. The identified biomarkers will include proteins, metabolites, and other characteristic biomolecules.
Year 1: During the discovery phase, all tests will be conducted by JaxBio and TAU with the aid of technical service providers. At this stage, microarray measurements will be performed on a commercial platform that will be purchased from Agilent / Illumina. All reagents needed for the test will be either purchased or produced in-house.
Years 2-3: Throughout the second phase of the project, a custom targeted microarray, HemaChip will be developed and used for all tests. The HemaChip and custom reagents will be distributed to partners' labs and all tests will be conducted at the clinical sites. Additional validation tests will be conducted by JaxBio and TAU, as needed.
Other Names:
|
| first-degree relatives of patients - Third stage Up to 400 first-degree relatives of patients (and in particular siblings). In order to allow a maximum follow-up period for at-risk subjects as part of the study, and to meet the recruitment goals, the screening, and enrollment can begin in the first stage of the trial. Follow-up patients, at-risk individuals for MM, and at-risk first-degree relatives will donate blood periodically according to the follow up plan. |
Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing
Classification of a broad spectrum of blood cancers based on detection of epigenetic biomarkers from genomic DNA, cell-free (cf) DNA, exosomal DNA, RNA and non-coding RNA. The identified biomarkers will include proteins, metabolites, and other characteristic biomolecules.
Year 1: During the discovery phase, all tests will be conducted by JaxBio and TAU with the aid of technical service providers. At this stage, microarray measurements will be performed on a commercial platform that will be purchased from Agilent / Illumina. All reagents needed for the test will be either purchased or produced in-house.
Years 2-3: Throughout the second phase of the project, a custom targeted microarray, HemaChip will be developed and used for all tests. The HemaChip and custom reagents will be distributed to partners' labs and all tests will be conducted at the clinical sites. Additional validation tests will be conducted by JaxBio and TAU, as needed.
Other Names:
|
| Healthy subjects - Discovery stage Healthy subjects that serve as controls are expected to donate blood a single time. Following this donation, their participation will end. At Tel-Aviv Sourasky Medical Center (TASMC) up to 50 bone marrow samples will be taken from healthy volunteers that will undergo hip or knee replacement surgery. |
Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing
Classification of a broad spectrum of blood cancers based on detection of epigenetic biomarkers from genomic DNA, cell-free (cf) DNA, exosomal DNA, RNA and non-coding RNA. The identified biomarkers will include proteins, metabolites, and other characteristic biomolecules.
Year 1: During the discovery phase, all tests will be conducted by JaxBio and TAU with the aid of technical service providers. At this stage, microarray measurements will be performed on a commercial platform that will be purchased from Agilent / Illumina. All reagents needed for the test will be either purchased or produced in-house.
Years 2-3: Throughout the second phase of the project, a custom targeted microarray, HemaChip will be developed and used for all tests. The HemaChip and custom reagents will be distributed to partners' labs and all tests will be conducted at the clinical sites. Additional validation tests will be conducted by JaxBio and TAU, as needed.
Other Names:
Diagnostic Test: Bone marrow sampling
as part of the discovery stage, bone marrow samples will be obtained at Tel-Aviv Sourasky Medical Center (TASMC) from up to 50 MM patients and up to 50 AML patients that undergo bone marrow aspiration as part of the standard care procedure. Additionally, up to 50 bone marrow samples will be taken from healthy volunteers that will undergo hip or knee replacement surgery.
|
Outcome Measures
Primary Outcome Measures
- Biomarker discovery [36 month]
define a set of differential epigenetic biomarkers that uniquely identify the following conditions: MM, pre-MM conditions (SMM and MGUS), HL, aggressive NHL (DLBCL, HGL, FL and MZL transformed to large cell lymphoma), FL, MZL, de novo AML, secondary AML, MDS and healthy subjects.
- Validation of Hemachip [36 month]
Validating the discovery platform (HemaChip) as a diagnostic tool for various blood cancers.
- Early detection for hematological malignancies [36 month]
Towards early detection - Patients, at risk of relapse tested periodically to evaluate early detection capability of the HemaChip.
- population screening for hematological malignancies [36 month]
Towards population screening - evaluate the sensitivity and specificity for screening in populations at risk for developing the investigated cancers: (i) elderly (>65 years old) at high risk to develop MM; (ii) first degree relatives of the conditions described above.
Eligibility Criteria
Criteria
Inclusion Criteria:
- General criteria for all study populations:
-
Male and female subjects ≥18 years of age
-
Ability to understand and willingness to sign a written informed consent document.
For Patients with blood cancers:
- Patients who have been diagnosed, have measurable disease, and/or are being monitored/followed up due to one of the following conditions: MM, pre-MM conditions (SMM and MGUS), HL, aggressive NHL (DLBCL, HGL, FL, and MZL transformed to large cell lymphoma), FL, MZL, de novo AML, secondary AML, MDS that did not yet undergo any treatment or surgery.
NOTE: Patients with transformed FL or MZL and patients with secondary AML that were treated for the primary disease prior to study enrollment are eligible.
For Healthy subjects:
-
First-degree relatives, spouses, and/or escorts of patients;
-
Elderly subjects - ≥ 65 years of age.
Exclusion Criteria:
-
Patients/subjects with current co-diagnosis of another type of cancer;
-
Patients/subjects with a known active or prior cancer (other than defined as study population), occurring within the last 2 years (even if considered to be in complete remission). Patients/subjects with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection;
-
Patients/subjects with active inflammatory autoimmune disease, treated or untreated with immunosuppressive/ immunomodulation agents;
-
Patients/subjects with known human immunodeficiency virus (HIV) positive;
-
Subjects that are likely to be noncompliant with the protocol, or felt to be unsuitable by the investigator for any other reason.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fakultni Nemocnice Olomouc (Fno) | Olomouc | Czechia | ||
| 2 | 8. Ethniko Kai Kapodistriako Panepistimio Athinon (Nkua) | Atene | Greece | ||
| 3 | Tel-Aviv Sourasky Medical Center (TASMC) | Tel Aviv | Israel | ||
| 4 | Santaros Klinikos | Vilnius | Lithuania |
Sponsors and Collaborators
- JaxBio Ltd
- Tel Aviv University
- FORSCHUNGSZENTRUM FUR MEDIZINTECHNIK UND BIOTECHNOLOGIE
- UNIVERZITA PALACKEHO V OLOMOUCI
- FAKULTNI NEMOCNICE OLOMOUC
- Vilnius University Hospital Santaros Klinikos
- PREDICTBY RESEARCH AND CONSULTING S.L.
- ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON
- Tel Aviv Medical Center
- UAB ORIENTOS
Investigators
- Study Chair: Yuval Prof. Ebenstein, PhD, Tel Aviv University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SANGUINE