Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasm, Residual

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

This study includes a total of 60 multiple myeloma patients, and peripheral blood will be collected at newly diagnosed, remission after 4 cycles of therapy, and, relapse stage.

10 mL of peripheral blood will be drawn from 60 multiple myeloma patients at diagnosis, 4 months post-induction, and at relapse, and cell-free DNA is then extracted and undergo bisulfite methylation sequencing.

plasma circulation DNA methylation sequencing

Gang An, PhD

Jian Cui, Bachelor

Gang An, PhD&MD

InsituteHBDH

1. To carry out research on minimal residual disease (MRD) monitoring in patients with multiple myeloma (MM) based on plasma circulating tumor DNA (ctDNA) methylation sequencing, which aims to explore new MRD detection methods for MM;
2. Carry out ctDNA-based methylation sequencing in newly diagnosed, remission, and, relapsed MM patients, to track the clonal evolution patterns; and explore the in the initial diagnosis-remission-relapse stage of MM, track the clonal evolution characteristics of methylation profiles in MM patients during the disease progression.

ctDNA Methylation Sequencing for Myeloma

Circulating Tumor DNA Methylation Sequencing for Multiple Myeloma Minimal Residual Disease Detection and Clonal Evolution Monitoring

The datasets generated during and/or analysed during the current study are available from the corresponding author at angang@ihcams.ac.cn on reasonable request.

When the peripheral blood samples required for the study have been collected

MethylGene Tech Co., Ltd. China

Institute of Hematology & Blood Diseases Hospital, China

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Genomic Instability

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Myotonic Dystrophy Type 1

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Trastuzumab

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

Atezolizumab

Alectinib

Ado-Trastuzumab Emtansine

Vemurafenib

Adenosine

Maytansine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Tyrosine Kinase Inhibitors

Tyrosine

MPDL3280A 1200mg IV infusion - 3 weekly until progression or unacceptable toxicity.

Or in combination with chemotherapy:

* For non-squamous: Cisplatin or Carboplatin plus pemetrexed \& MPDL3280A - 3 weekly for 4 cycles followed by MPDL3280A and pemetrexed 3 weekly until progression or unacceptable toxicity or completion of a total of 35 cycles. MPDL3280A will then continue 3 weekly until progression or unacceptable toxicity.
* For squamous: Carboplatin plus paclitaxel \& MPDL3280A - 3 weekly for 4 cycles followed by MPDL3280A 3 weekly until progression or unacceptable toxicity.

Trastuzumab emtansine (T-DM1) 3.6mg/kg - 3 weekly until PD IV infusion

Intravenous (IV) infusion, as monotherapy of in combination with chemotherapy

MPDL3280A

Powder for concentrate for solution for infusion

Trastuzumab emtansine

Charles Swanton

DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who relapse with NSCLC (clinical trials.gov ref. NCT02183883). .

The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal actionable mutation) is associated with PFS.

Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous or squamous).

Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib respectively.

DARWIN II will include extensive exploratory biomarker analysis to investigate a number of genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help guide future clinical trial design.

DARWIN II is an exploratory phase II study examining the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy.

It will examine how clonal dominance and intratumour heterogeneity influence outcomes after treatment, offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1. These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC. The relationship between intratumour heterogeneity and cfDNA/CTCs will also be explored in DARWIN II, which may develop tools for patient selection and monitoring to be examined further in future studies. Results from DARWIN II will help to identify a biomarker for anti-PD-L1 therapy which could be used for patient stratification in future phase III trials of molecules targeting this T-cell inhibitory checkpoint. DARWIN II will also provide preliminary data on efficacy of MPDL3280A, which could be used to design randomised studies.

This is a multicentre non-randomised phase II study based on patients with relapsed NSCLC, who have provided a biopsy sample at the time of relapse.

The study arms:

* Arm 1: Patients without an actionable mutation - MPDL3280A (atezolizumab) monotherapy or in combination with chemptherapy
* Arm 2: BRAFV600 - vemurafenib
* Arm 3: ALK/RET gene rearrangement - alectinib
* Arm 4: HER2 Amplification - trastuzumab emtansine

Arms 2-4 are closed to further recruitment as of 25th May 2021.

Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity

Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity - DARWINII

Defined as the period between the date of registration to the date of subsequent progression or death (whichever occurs first)

Investigator-assessed according to RECISTv1.1 and irRC (Arm 1 only)

Period between first complete response or partial response until the first date recurrence or progressive disease, assessed up to 84 months

Dose reductions, interruptions, modifications and exposure

Interrogation of recurrence and progression biopsies to decipher the molecular basis for resistance in combination with analyses of CTCs/cfDNA as well as CT imaging heterogeneity analyses

Hoffmann-La Roche

University College, London

Chromosome Aberrations

Neoplastic Processes

Gang An, PhD&amp;amp;MD

Jian Cui, MBBS

The presence of minimal residual disease (MRD) is an important prognostic factor for multiple myeloma, while copy number variation (CNV) is a widely accepted biomarker used for multiple myeloma (MM). Detecting MRD and monitoring clonal evolution by monitoring CNV using low-pass whole genome sequencing is promising due to its high analytical sensitivity. To evaluate the correlation between MRD detected by flow cytometry and low-pass whole genome sequencing, nearly 200 samples were collected for this study. We applied ultrasensitive chromosomal aberrations detection to detect CNV for each patient. The follow-up samples were then collected and sequencing used the same method.

Bone marrow mononuclear cells from multiple myeloma patients

Detecting Minimal Residual Diseases (MRD) and Monitoring Clonal Evolution Using Ultrasensitive Chromosomal Aberrations Detection (UCAD) in Multiple Myeloma

Clinical Utility of Ultrasensitive Chromosomal Aberrations Detection (UCAD) for Detecting Minimal Residual Disease (MRD) and Monitoring Clonal Evolution by Low-Pass Whole Genome Sequencing in Multiple Myeloma

Professor

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

María Díez Campelo, PhD MD

Mónica del Rey González, PhD

Francesc Solé, PhD

David Valcárcel Ferreiras, PhD

Felipe López Cardoso, PhD

María Díez Campelo, PhD

Sandra Muntión Olave, PhD

Myelodysplastic Syndromes (MDS) are heterogeneous clonal diseases characterized by difficult diagnosis, complex prognostic stratification and unsatisfactory treatment. Based on that, UMBRELLA SUMMA aims to provide better clinical management and personalized medicine to MDS patients in Spain through improving diagnosis (1), prognosis (2 and 3), and treatment (2), and facilitating future investigations (4) of the disease.

More concretely, we propose: 1. The application of new technologies such as Optical Genome Mapping (OGM) in the diagnosis of those MDS cases whose cytogenetic alterations cannot be identify by other methods, as well as the implementation of this technology using peripheral blood avoiding more invasive methods for patients. 2. To provide all Spanish Group of MDS (GESMD) members who require it with the newly prognostic stratification of their patients (IPSS-M) by making Next Generation Sequencing (NGS) accessible for all of them. 3. Validate and improve a new prognostic system (AIPSS-MDS) previously developed within the GESMD, thanks to artificial intelligence, one of the tools with the most projection in the field of medicine currently. 4. To build and register ISCIII collections of cells, genetic material and/or plasma from all prospective MDS patients.

On the other hand, the dynamics of coexisting mutations in a specific context of chromosomal abnormalities could be defining the clinical fate of each patient. Based on that, the IBSAL team recently proposed three models of MDS evolution based on NGS data from three different cytogenetic subgroups: normal karyotype, trisomy 8 and 5q deletion. The IBSAL proposal aims to deepen into the pathophysiological mechanisms of MDS evolution in these three models through in vitro and in vivo functional studies and single-cell multiomics approaches.

Mononuclear cells, DNA, RNA and plasma from bone marrow and/or peripheral blood of MDS patients (MNC;MSC)

Unified platforM for a Better integRal Evaluation of MyeLodyspLastic Syndromes in SpAin-Strategy for Unraveling Personalized genoMic Medicine in Public heAlth System (UMBRELLA-SUMMA)

Optical Genome Mapping will be used to determine the presence of structural variant and complex rearrangements not detected by other conventional techniques

Next Generation Sequencing will be use to define the IPSS-M (the International Molecular Prognostic Scoring System) in patients with MDS

The AIPSS-MDS (Artificial Intelligence Prognostic Scoring System for MDS) model will be validated to provide a personalized risk estimate for each individual patient

To build and register ISCIII collections of viable samples (PB and BM cells), genetic material and/or plasma from all prospective MDS patients

Carlos III Health Institute

Instituto de Investigación Biomédica de Salamanca

Monoclonal Gammopathy of Undetermined Significance

Waldenstrom Macroglobulinemia

Lymphatic Diseases

Part of the patients will be retrospectively enrolled (learning sample) and part prospectively (validation sample)

Patient evaluation at the time of diagnosis and during the disease course using highly sensitive techniques

MRD and clonal evolution

Marzia Varettoni

Multicenter retrospective and prospective observational study including patients with WM or IgM-MGUS evaluated at the time of diagnosis and during the disease course using highly sensitive techniques.

Multicenter retrospective and prospective observational study including patients with WM or IgM-MGUS evaluated at the time of diagnosis and during the disease course using highly sensitive techniques such as flow cytometry, real time quantitative PCR (RT-qPCR), digital droplet PCR (dd-PCR) and NGS, in order to: evaluate the mutational status on genomic DNA or cell-free DNA and compare the results to assess the most reliable source for mutation studies; perform and compare molecular and flow cytometry analyses on bone marrow, peripheral blood (both analyses), plasma and urine samples (only molecular analysis) to assess the best source for diagnosis and MRD monitoring.

Peripheral blood, Bone marrow and Urine collected at Baseline, Before treatment, after treatment, at 12 months follow up, at 24 months follow up and at 60 months follow up

Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS

Non-invasive Diagnostics and Monitoring of Minimal Residual Disease and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM Monoclonal Gammopathy of Undetermined Significance

To demonstrate that the rate of mutations of MYD88 (L265P) and/or CXCR4 (S338X) detected in peripheral blood and/or urine show a negligible difference with the rate of mutations detected in bone marrow samples (BM, gold standard)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ctDNA Methylation Sequencing for Myeloma	NCT05578625	Multiple Myelom...	plasma circulat...	18 Years - 75 Years	Institute of Hematology & Blood Diseases Hospital, China
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity	NCT02314481	Non-small Cell ...	MPDL3280A Vemurafenib Alectinib Trastuzumab emt...	18 Years -	University College, London
Detecting Minimal Residual Diseases (MRD) and Monitoring Clonal Evolution Using Ultrasensitive Chromosomal Aberrations Detection (UCAD) in Multiple Myeloma	NCT06302699	Multiple Myelom...		18 Years -	Institute of Hematology & Blood Diseases Hospital, China
ctDNA Methylation Sequencing for Myeloma	NCT05578625	Multiple Myelom...	plasma circulat...	18 Years - 75 Years	Institute of Hematology & Blood Diseases Hospital, China
Unified platforM for a Better integRal Evaluation of MyeLodyspLastic Syndromes in SpAin-Strategy for Unraveling Personalized genoMic Medicine in Public heAlth System (UMBRELLA-SUMMA)	NCT06379945	Myelodysplastic...		18 Years -	Instituto de Investigación Biomédica de Salamanca
Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS	NCT03521596	Waldenstrom Mac...	MRD and clonal ...	18 Years -	Fondazione Italiana Linfomi - ETS
Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS	NCT03521596	Waldenstrom Mac...	MRD and clonal ...	18 Years -	Fondazione Italiana Linfomi - ETS

Spots Global Cancer Trial Database for clonal evolution