Early Detection and Screening of Hematological Malignancies - SANGUINE

Recruiting

• Conditions: Hematologic Malignancy
• Interventions: Diagnostic Test: Blood sampling for HemaChip screening/diagnostic testing; Diagnostic Test: Bone marrow sampling

• Registration Number: NCT05735704
• Lead Sponsor: JaxBio Ltd

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), diffuse large B cell lymphoma (DLBCL), Follicular lymphoma (FL), Marginal Zone lymphomas (MZL), acute myeloid leukemia (AML)\*, myelodysplastic syndrome (MDS), subjects at risk and control subjects with no malignant disease.

\*Patients with a diagnosis of acute promyelocytic leukemia (APL) are not included

Detailed Description

Subjects will be screened for eligibility and then, after signing an Informed Consent Form, the first peripheral blood sample 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, DLBCL, FL, MZL, AML, MDS, and control subjects with no malignant disease.

In the second stage, at least 250 patients with MM 250 patients with NHL, at least 100 patients with each of the remaining hematological malignancies mentioned above, and control subjects with no malignant disease will be tested. Out of these patients, AML, lymphoma and MM patients will be followed up at the clinical sites. Periodic sampling will be defined according to disease type and progression rate. Blood and plasma samples will be stored in the clinical sites until relapse diagnosis. At this stage, blood samples will be analyzed retrospectively on the HemaChip. The screening, enrollment, and blood collection can begin in the first stage of the trial, to allow a maximum follow-up period, as part of the study, and to meet the recruitment goals.

The last stage consists of the screening of a larger group of subjects at risk of developing MM / lymphoproliferative disorder. This stage will include 400 elderly patients (\>65 years old) and 500 first-degree relatives of patients (and in particular siblings). The screening, enrollment, and sample collection can begin in the first stage of the trial, to allow a maximum period for at-risk subjects cohort to meet the recruitment goals.

In all stages, the age and sex-matched subgroups will be considered and matched.

During the follow-up period, demographic and baseline parameters including sex, age, race, height and weight, medical history, smoking status, details of initial diagnosis and treatment history, concomitant medications as well as adverse events (AEs) of special interest, (serious) AEs related to study procedures, treatment for the disease, disease response and survival status will be collected (as applicable).

Study Timeline

• Study Start: 2023-01-30
• Study First Submitted: 2023-01-31
• Study First Submitted QC: 2023-02-09
• Study First Posted: 2023-02-21
• Status Verified: 2024-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-26
• Primary Completion: 2026-01-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3000

Inclusion Criteria

General criteria for all study populations:

1. Male and female subjects ≥18 years of age
2. Ability to understand and willingness to sign a written informed consent document.

For Patients with hematological malignancies:

1. 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, DLBCL, FL, MZL, AML, MDS that did not yet undergo any treatment.

NOTE:

Patients diagnosed with DLBCL that is transformed from FL or MZL, and patients diagnosed with AML secondary to MDS or MPN, who were treated for their primary disease (FL/MZL/MDS/MPN) before study enrollment, are eligible.

For subjects at risk for developing the investigated hematological malignancies:

1. First-degree relatives; AND /OR
2. Elderly subjects ≥ 65 years of age.

Exclusion Criteria

1. Patients/subjects with current co-diagnosis of another type of cancer;
2. 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;
3. Patients with a diagnosis of acute promyelocytic leukemia (APL)
4. Patients/subjects with active inflammatory autoimmune disease that requires treatment with immunosuppressive/ immunomodulation agents;
5. Patients/subjects with known human immunodeficiency virus (HIV) positive;
6. Patients/subjects with known active Hepatitis A/B/C or past hepatitis C;
7. Subjects that are likely to be noncompliant with the protocol, or felt to be unsuitable by the investigator for any other reason.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with Hematological Malignancies - Discovery stage	Blood sampling for HemaChip screening/diagnostic testing	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, MZL, AML, MDS. NOTE: Patients diagnosed with DLBCL that is transformed from FL or MZL, and patients diagnosed with AML secondary to MDS or MPN, that were treated for their primary disease (FL/MZL/MDS/MPN) prior to study enrollment, are eligible. For patients, it is expected, after signing the informed consent, 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.
Patients with Hematological Malignancies - Second stage	Blood sampling for HemaChip screening/diagnostic testing	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 hematological malignancies mentioned above will be tested. Out of these patients, AML, lymphoma and MM patients will be followed-up at the clinical sites. Periodic sampling will be defined according to disease type and progression rate. Blood and plasma samples will be stored in the clinical sites until relapse diagnosis. At this stage, blood samples will be analyzed retrospectively on the HemaChip. The screening, enrollment, and sample collection can begin in the first stage of the trial, in order to allow a maximum follow-up period for at-risk subjects as part of the study and to meet the recruitment goals.
subjects at risk of developing MM / lymphoproliferative disorder - Third stage	Blood sampling for HemaChip screening/diagnostic testing	The last stage consists of screening of a larger group of subjects at risk of developing MM / lymphoproliferative disorder. This stage will include 400 elderly patients (\>65 years old) and 500 first-degree relatives of patients (and in particular siblings). The screening, enrollment, and sample collection can begin in the first stage of the trial, in order to meet the recruitment goals. Follow-up patients, at-risk individuals for MM, and at-risk first-degree relatives will donate blood periodically according to the follow-up plan.
Control subjects with no malignant disease- Discovery stage	Blood sampling for HemaChip screening/diagnostic testing	Control subjects with no malignant disease 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.
Control subjects with no malignant disease- Discovery stage	Bone marrow sampling	Control subjects with no malignant disease 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.

Primary Outcome Measures

Name	Time	Method
Validation of Hemachip	36 month	Validating the discovery platform (HemaChip) as a diagnostic tool for various blood cancers.
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.
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.
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.

Trial Locations

Locations (4)

Fakultni Nemocnice Olomouc (Fnol); 🇨🇿 Olomouc, Czechia

National and Kapodistrian University of Athens (NKUA); 🇬🇷 Atene, Greece

Vilnus University Hospital Santaros Klinikos (VULSK); 🇱🇹 Vilnius, Lithuania

Tel-Aviv Sourasky Medical Center (TASMC); 🇮🇱 Tel Aviv, Israel