Leukemia, Myeloid, AcuteNCT06785077
Genetic Landscape in Women with Metastatic Ovarian Cancer Before and During Treatment with PARP Inhibitors
A study testing buccal cells, bone marrow cells and peripheral blood cells in people with Leukemia, Myeloid, Acute and Myeloid Dysplasia, run by European Institute of Oncology at 1 site in Italy.
Trial summary
Therapy related acute myeloid leukemia and myelodysplasia (t-MN) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple cycles of platinum-based chemotherapy during the course of their disease. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Leukemia, Myeloid, Acute, Myeloid Dysplasia, Ovarian Epithelial Cancer
- What is being tested?
- buccal cells, bone marrow cells and peripheral blood cells
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 1 siteItaly
- Study dates
- 2 Oct 2020to 30 Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy.
Who cannot join
- Presence of blood cell count abnormalities before PARP inhibitor treatment;
- Bone marrow infiltration by EOC cells.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Istituto Europeo di Oncologia
Milan, 20141
Federica Gigli, +390257489538, federica.gigli@ieo.it
About this study
Official title: Mutational Landscape of Women Suffering from Metastatic Ovarian Cancer Before Poly (ADP-ribose) Polymerase Inhibitors Maintenance Treatment and During Treatment. Incidence of Therapy-related Hematological Neoplasms.
Therapy related acute myeloid leukemia and myelodysplasia (t-MN) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple cycles of platinum-based chemotherapy during the course of their disease. An epidemiological analysis published in 2011 (Gynecologic Oncology) showed that the overall incidence of t-AML is 0.17%, with a median latency to development of leukemia of 4 years (range 0-27 years).
Inhibition of PARP is a potential synthetic lethal therapeutic strategy for the treatment of cancers characterized by specific DNA repair defects, such as those that harbor a BRCA1 or BRCA2 (BRCA1/2) mutation and are therefore deficient in homologous recombination repair. In homologous recombination-deficient tumors, PARP inhibition eliminates an alternative DNA repair pathway essential for maintaining viability, leading to tumor cell death. The estimated prevalence of BRCA1/2 mutations in V2 03/06/2021 2 patients with newly diagnosed high-grade serous ovarian cancer is 20-25% and it might be higher in patients with platinum-sensitive, relapsed ovarian cancer. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations.
Read more
Our hypothesis is that these patients are carriers of clonal hematopoiesis of indeterminate potential (CHIP) before treatment with PARPi. CHIP refers to the presence of clonal population(s) of hematopoietic cells with somatic mutations in genes associated with hematological malignancies (e.g. DNMT3A, ASXL1, TET2, TP53 and others), in the absence of morphological evidence of disease.
The proposed study will address the hypothesis that platinum-based chemotherapy may promote the onset of newly developed mutated clones and clonal selection of hematopoietic stem cells harboring somatic mutations.
Moreover, the concomitant presence of germline mutations in cancer predisposing genes might increase the pool of pre-existing hematopoietic clones and/or favor the accumulation of subsequent somatic mutations.
In this context, the inhibition of PARP-mediated repair of DNA lesions created by chemo or radiotherapy can further favor t-MN development.
Read the detailed description
Analysis on peripheral blood
After withdrawal, the following analysis will be performed on the peripheral blood samples:
- morphological evaluation with potential identification of dysplastic changes involving one or more hematopoietic lineage suggesting or not myelodysplastic syndrome or acute leukemias;
- cytofluorimetric analysis of mononuclear cell phenotype to identify possible abnormalities in the differentiation pathway and the presence of blasts.
Immune phenotyping will be performed by 10 colors multiparametric FACS analysis (Navios, Beckman Coulter). Myeloid cell maturation and presence of progenitors/blasts will be assessed in blood samples with the following markers:
- CD66b, CD11b, CD16, CD38, CD34, CD13, CD14, CD33, CD45, HLA-DR
- CD34, CD117, CD45, CD10, CD19, CD13, CD33, CD64, CD36, CD71 The rest of the analyses will be performed on thawed mononuclear cells. For each staining, a marker of cell viability will be used (Live/Dead, Thermo Fisher Scientific). Parameters will be chosen based on previous results obtained from genome and phenotype analysis.
The impact of the treatment on different cell populations will be measured by comparing patients.
Analysis on bone marrow
Bone marrow material will be withdrawn by bone marrow aspirate and bone marrow biopsy and the following analysis will be performed:
- Bone marrow aspirate:
- morphological evaluation with potential identification of dysplastic changes involving one or more hematopoietic lineage suggesting or not myelodysplastic syndrome or acute leukemias;
- cytofluorimetric analysis of mononuclear cell phenotype to identify possible abnormalities in the differentiation pathway and the presence of blasts ;
- cytogenetic and FISH analysis to identify the possible presence of chromosomal abnormalities induced by the previous or ongoing treatment. Heparin bone marrow samples will be sent to the Hematology Lab and will be freshly processed following the standard diagnostic procedures. For cytogenetic analysis, at least 10x106 cells will be cultured for 24/48h and will be processed following a standard protocol for karyotype analysis. The metaphases will be stained with QFQ banding and will be analyzed with Cytovysion Software (Leica). At least 20 metaphases will be analyzed and reported. For FISH analysis, at least 500 ul of bone marrow sample will be processed following a standard protocol. For FISH analysis, the panel of probes routinely used in the hematology laboratory for myelodysplastic patients will be used: EGR1/D5S630 for monosomy/deletion 5q Vysis Probe D7S486/CEN7 for monosomy7/deletion 7q Vysis Probe MECOM/EVI1 for inv(3)/t(3;3) Cytocell Probe D20S108 for deletion 20q Vysis Probe CEN8 for trisomy 8 Vysis Probe Each probe will be evaluated on 200 nuclei and will be reported with abnormalities if they are above our internal cut-off.
- Paraffin embedded sections from bone marrow biopsy:
- morphological evaluation;
- immunohistochemistry.
Genetic analysis
The types of genetic analysis will be performed during the course of the study are:
- analysis of germline variants. To identify germline genetic variants that may predispose ovarian cancer patients to develop t-MN, an in-house developed personalized genetic panel, the Myelo Panel, will be used. The panel will target cancer predisposing genes, including those most frequently associated with the risk of development of hematological tumors, AML drivers, actionable genes and pharmacogenomics SNPs ;
- analysis of CHIP. In order to detect the presence of CHIP in the enrolled patients and to monitor the evolution of the CHIP clones following treatment with PARP inhibitor, it will be use high-sensitive NGS sequencing technology: Unique Molecular Barcoding (UMI) sequencing. The UMI-sequencing protocol, coupled to custom target enrichment, allows to detect mutations with a frequency as low as 0.1%.A personalized genetic panel containing the 80 most frequently mutated genes in CHIP will be used. ABL1 BRCC3 ETV6 HIST1H1C MPL PIK3CA SETD2 STAT3 ASXL1 CALR EZH2 IDH1 MYD88 PPM1D SETDB1 SUZ12 ASXL2 CARD11 TENT5C (FAM46C) IDH2 NF1 PRDM1 SF1 TET1 ATM CBL FBXW7 IKZF1 NOTCH1 PTPN11 SF3B1 TET2 ATRX CBLB FLT1 JAK2 NOTCH2 RAD21 SH2B3 TNFAIP3 AXL CEBPA FLT3 JAK3 NOTCH3 RHEB SMAD4 TNFRSF14 BCOR CREBBP FOXP1 KDM6A NPM1 RICTOR SMC1A TP53 BCORL1 CUX1 GATA2 KIT NRAS RIT1 SMC3 U2AF1 BIRC3 DNMT3A GNAS KMT2D (MLL2) PAX5 RUNX1 SRSF2 WT1 BRAF EP300 GNB1 KRAS PHF6 SETBP1 STAG2 ZRSR2
- analysis of mutations associated with myeloid malignancies. To identify the genomic landscape of the developed t-MN, the mutational status of 69 genes potentially involved in the development of myeloid disease will be assessed using a commercially available diagnostic panel: Oncomine Myeloid Research Assay (Thermo Fisher Scientific, see Appendix 5). In parallel, the results obtained will be compared with the in-house developed custom gene panel, the Myelo Panel, which also includes genes most frequently associated with the risk of developing hematological malignancies, AML drivers, actionable genes and pharmacogenomic SNPs. Analysis Timeline For each enrolled patient, the detailed analysis below will be performed. Before PARP inhibitor treatment (as first line and as maintenance therapy) Buccal cells:
- custom myeloid gene panel (Myelo-Panel) to identify germline mutations predisposing to cancer development (Thermo Fisher Scientific) Bone marrow cells (optional, for comparison, only in a limited number of patients):
- morphological analysis
- immunophenotype
- cytogenetics/FISH
- analysis of CHIP by custom gene panel and high sensitivity NGS Peripheral blood cells:
- analysis of CHIP by custom gene panel and high sensitivity NGS Bone marrow biopsy (optional, for comparison, only in a limited number of patients):
- histology
- immunohistochemistry Every 6 months during PARP inhibitor treatment Peripheral blood cells:
- analysis of CHIP by custom gene panel and high sensitivity NGS Appearance of blood count abnormalities and/or haematological neoplasms During PARP inhibitor maintenance treatment, patients will be monitored monthly with clinical and blood count examination. In case of appearance of blood count abnormalities (CTCAE grade ≥ 2 and/or platelets<100.000/mmc), involving at least one hematopoietic subpopulation, the drug will be suspended and blood cell counts evaluated every 2 weeks. In case of recovery the drug will be reintroduced. In case of stability or further deterioration, bone marrow and peripheral blood examinations (analysis detailed below) will be performed after 4-8 weeks from PARP inhibitor interruption at least, unless the worsening of the blood counts is so fast that it requires a bone marrow evaluation before. At appearance of blood count abnormalities, the following analysis will be perform: Bone marrow cells:
- morphological analysis
- immunophenotype
- cytogenetics/FISH
- analysis of mutations by both Oncomine Myeloid Research Panel and our custom Myelo-Panel (Thermo Fisher Scientific)
- analysis of CHIP by custom gene panel and high sensitivity NGS Bone marrow biopsy:
- histology
- immunohistochemistry
- Being tested
- buccal cells, bone marrow cells, peripheral blood cells, bone marrow biopsy
- Keywords
- PARP inhibitors (PARPi) Treatment, gene panels, clonal hematopoiesis of indeterminate potential (CHIP), Analysis on peripheral blood, Analysis on bone marrow, Genetic analysis
- Medical subject headings
- Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
buccal cellsProcedure or surgery
custom myeloid gene panel (Myelo-Panel) to identify germline mutations predisposing to cancer development (Thermo Fisher Scientific)
bone marrow cellsProcedure or surgery
Bone marrow cells (optional, for comparison, only in a limited number of patients):
- morphological analysis
- immunophenotype
- cytogenetics/FISH
- analysis of CHIP by custom gene panel and high sensitivity NGS
peripheral blood cellsProcedure or surgery
analysis of CHIP by custom gene panel and high sensitivity NGS
bone marrow biopsyProcedure or surgery
Bone marrow biopsy (optional, for comparison, only in a limited number of patients):
- histology
- immunohistochemistry
| Study group | Role | What they receive |
|---|---|---|
| advanced ovarian cancer patient | Experimental | Women with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy. Receives: Procedure: buccal cells; Procedure: bone marrow cells; Procedure: peripheral blood cells; Procedure: bone marrow biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the events and determination of their incidence in study patient's population:
The study is descriptive in nature and no formal statistical testing is necessary or applicable.
- Cell blood count abnormalities
- Morphological alterations allowing a diagnosis of myelodysplastic syndrome or acute myeloid leukemia
- Chromosomal abnormalities
- Clonal hematopoiesis and extent of the expansion and evolution of the CHIP clones induced by PARP inhibitors.
One of the primary objectives is to estimate the proportion of patients with stable abnormalities in hematologic counts. A patient is defined as having stable abnormalities in hematologic counts if the status "CTCAE grade ≥ 2 and/or platelets <100,000/mmc" persists for at least two weeks.The 90% confidence interval of the proportion of patients with stable abnormalities in hematologic counts will be calculated using the exact one-sided binomial test.
Measured: 8 years
Secondary outcomes (1)
Survival data evaluation
- Overall survival (OS)
- Progression free survival (PFS) Progression free survival (PFS) will be defined as the time from initiation of PARP-inhibitor treatment to objective disease progression on imaging or death from any cause. Overall survival (OS) will be defined as the time from initiation of PARP-inhibitor treatment to death from any cause.
Both PFS and OS will be estimated using the Kaplan-Meier method.
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2025
- Study start2 Oct 2020
- Primary completion30 Apr 2028 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 157 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Federica Gigli, Principal investigator, Istituto Europeo di Oncologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06785077
- Sponsor's protocol ID
- IEO 1353
- Status last verified
- Mar 2024
- First submitted
- 5 Dec 2024
- Last updated
- 20 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mutational Landscape of Women Suffering from Metastatic Ovarian Cancer Before Poly (ADP-ribose) Polymerase Inhibitors Maintenance Treatment and During Treatment. Incidence of Therapy-related Hematological Neoplasms.
- ClinicalTrials.gov ID
- NCT06785077
- Acronym / sponsor ID
- IEO 1353
- Keywords
- PARP inhibitors (PARPi) Treatment, gene panels, clonal hematopoiesis of indeterminate potential (CHIP), Analysis on peripheral blood, Analysis on bone marrow, Genetic analysis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 157 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 2 Oct 2020 (actual)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 20 Jan 2025 (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.
Therapy related acute myeloid leukemia and myelodysplasia (t-MN) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple cycles of platinum-based chemotherapy during the course of their disease. An epidemiological analysis published in 2011 (Gynecologic Oncology) showed that the overall incidence of t-AML is 0.17%, with a median latency to development of leukemia of 4 years (range 0-27 years).
Inhibition of PARP is a potential synthetic lethal therapeutic strategy for the treatment of cancers characterized by specific DNA repair defects, such as those that harbor a BRCA1 or BRCA2 (BRCA1/2) mutation and are therefore deficient in homologous recombination repair. In homologous recombination-deficient tumors, PARP inhibition eliminates an alternative DNA repair pathway essential for maintaining viability, leading to tumor cell death. The estimated prevalence of BRCA1/2 mutations in V2 03/06/2021 2 patients with newly diagnosed high-grade serous ovarian cancer is 20-25% and it might be higher in patients with platinum-sensitive, relapsed ovarian cancer. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations.
Our hypothesis is that these patients are carriers of clonal hematopoiesis of indeterminate potential (CHIP) before treatment with PARPi. CHIP refers to the presence of clonal population(s) of hematopoietic cells with somatic mutations in genes associated with hematological malignancies (e.g. DNMT3A, ASXL1, TET2, TP53 and others), in the absence of morphological evidence of disease.
The proposed study will address the hypothesis that platinum-based chemotherapy may promote the onset of newly developed mutated clones and clonal selection of hematopoietic stem cells harboring somatic mutations.
Moreover, the concomitant presence of germline mutations in cancer predisposing genes might increase the pool of pre-existing hematopoietic clones and/or favor the accumulation of subsequent somatic mutations.
In this context, the inhibition of PARP-mediated repair of DNA lesions created by chemo or radiotherapy can further favor t-MN development.
Detailed description
Analysis on peripheral blood
After withdrawal, the following analysis will be performed on the peripheral blood samples:
- morphological evaluation with potential identification of dysplastic changes involving one or more hematopoietic lineage suggesting or not myelodysplastic syndrome or acute leukemias;
- cytofluorimetric analysis of mononuclear cell phenotype to identify possible abnormalities in the differentiation pathway and the presence of blasts.
Immune phenotyping will be performed by 10 colors multiparametric FACS analysis (Navios, Beckman Coulter). Myeloid cell maturation and presence of progenitors/blasts will be assessed in blood samples with the following markers:
- CD66b, CD11b, CD16, CD38, CD34, CD13, CD14, CD33, CD45, HLA-DR
- CD34, CD117, CD45, CD10, CD19, CD13, CD33, CD64, CD36, CD71 The rest of the analyses will be performed on thawed mononuclear cells. For each staining, a marker of cell viability will be used (Live/Dead, Thermo Fisher Scientific). Parameters will be chosen based on previous results obtained from genome and phenotype analysis.
The impact of the treatment on different cell populations will be measured by comparing patients.
Analysis on bone marrow
Bone marrow material will be withdrawn by bone marrow aspirate and bone marrow biopsy and the following analysis will be performed:
- Bone marrow aspirate:
- morphological evaluation with potential identification of dysplastic changes involving one or more hematopoietic lineage suggesting or not myelodysplastic syndrome or acute leukemias;
- cytofluorimetric analysis of mononuclear cell phenotype to identify possible abnormalities in the differentiation pathway and the presence of blasts ;
- cytogenetic and FISH analysis to identify the possible presence of chromosomal abnormalities induced by the previous or ongoing treatment. Heparin bone marrow samples will be sent to the Hematology Lab and will be freshly processed following the standard diagnostic procedures. For cytogenetic analysis, at least 10x106 cells will be cultured for 24/48h and will be processed following a standard protocol for karyotype analysis. The metaphases will be stained with QFQ banding and will be analyzed with Cytovysion Software (Leica). At least 20 metaphases will be analyzed and reported. For FISH analysis, at least 500 ul of bone marrow sample will be processed following a standard protocol. For FISH analysis, the panel of probes routinely used in the hematology laboratory for myelodysplastic patients will be used: EGR1/D5S630 for monosomy/deletion 5q Vysis Probe D7S486/CEN7 for monosomy7/deletion 7q Vysis Probe MECOM/EVI1 for inv(3)/t(3;3) Cytocell Probe D20S108 for deletion 20q Vysis Probe CEN8 for trisomy 8 Vysis Probe Each probe will be evaluated on 200 nuclei and will be reported with abnormalities if they are above our internal cut-off.
- Paraffin embedded sections from bone marrow biopsy:
- morphological evaluation;
- immunohistochemistry.
Genetic analysis
The types of genetic analysis will be performed during the course of the study are:
- analysis of germline variants. To identify germline genetic variants that may predispose ovarian cancer patients to develop t-MN, an in-house developed personalized genetic panel, the Myelo Panel, will be used. The panel will target cancer predisposing genes, including those most frequently associated with the risk of development of hematological tumors, AML drivers, actionable genes and pharmacogenomics SNPs ;
- analysis of CHIP. In order to detect the presence of CHIP in the enrolled patients and to monitor the evolution of the CHIP clones following treatment with PARP inhibitor, it will be use high-sensitive NGS sequencing technology: Unique Molecular Barcoding (UMI) sequencing. The UMI-sequencing protocol, coupled to custom target enrichment, allows to detect mutations with a frequency as low as 0.1%.A personalized genetic panel containing the 80 most frequently mutated genes in CHIP will be used. ABL1 BRCC3 ETV6 HIST1H1C MPL PIK3CA SETD2 STAT3 ASXL1 CALR EZH2 IDH1 MYD88 PPM1D SETDB1 SUZ12 ASXL2 CARD11 TENT5C (FAM46C) IDH2 NF1 PRDM1 SF1 TET1 ATM CBL FBXW7 IKZF1 NOTCH1 PTPN11 SF3B1 TET2 ATRX CBLB FLT1 JAK2 NOTCH2 RAD21 SH2B3 TNFAIP3 AXL CEBPA FLT3 JAK3 NOTCH3 RHEB SMAD4 TNFRSF14 BCOR CREBBP FOXP1 KDM6A NPM1 RICTOR SMC1A TP53 BCORL1 CUX1 GATA2 KIT NRAS RIT1 SMC3 U2AF1 BIRC3 DNMT3A GNAS KMT2D (MLL2) PAX5 RUNX1 SRSF2 WT1 BRAF EP300 GNB1 KRAS PHF6 SETBP1 STAG2 ZRSR2
- analysis of mutations associated with myeloid malignancies. To identify the genomic landscape of the developed t-MN, the mutational status of 69 genes potentially involved in the development of myeloid disease will be assessed using a commercially available diagnostic panel: Oncomine Myeloid Research Assay (Thermo Fisher Scientific, see Appendix 5). In parallel, the results obtained will be compared with the in-house developed custom gene panel, the Myelo Panel, which also includes genes most frequently associated with the risk of developing hematological malignancies, AML drivers, actionable genes and pharmacogenomic SNPs. Analysis Timeline For each enrolled patient, the detailed analysis below will be performed. Before PARP inhibitor treatment (as first line and as maintenance therapy) Buccal cells:
- custom myeloid gene panel (Myelo-Panel) to identify germline mutations predisposing to cancer development (Thermo Fisher Scientific) Bone marrow cells (optional, for comparison, only in a limited number of patients):
- morphological analysis
- immunophenotype
- cytogenetics/FISH
- analysis of CHIP by custom gene panel and high sensitivity NGS Peripheral blood cells:
- analysis of CHIP by custom gene panel and high sensitivity NGS Bone marrow biopsy (optional, for comparison, only in a limited number of patients):
- histology
- immunohistochemistry Every 6 months during PARP inhibitor treatment Peripheral blood cells:
- analysis of CHIP by custom gene panel and high sensitivity NGS Appearance of blood count abnormalities and/or haematological neoplasms During PARP inhibitor maintenance treatment, patients will be monitored monthly with clinical and blood count examination. In case of appearance of blood count abnormalities (CTCAE grade ≥ 2 and/or platelets<100.000/mmc), involving at least one hematopoietic subpopulation, the drug will be suspended and blood cell counts evaluated every 2 weeks. In case of recovery the drug will be reintroduced. In case of stability or further deterioration, bone marrow and peripheral blood examinations (analysis detailed below) will be performed after 4-8 weeks from PARP inhibitor interruption at least, unless the worsening of the blood counts is so fast that it requires a bone marrow evaluation before. At appearance of blood count abnormalities, the following analysis will be perform: Bone marrow cells:
- morphological analysis
- immunophenotype
- cytogenetics/FISH
- analysis of mutations by both Oncomine Myeloid Research Panel and our custom Myelo-Panel (Thermo Fisher Scientific)
- analysis of CHIP by custom gene panel and high sensitivity NGS Bone marrow biopsy:
- histology
- immunohistochemistry
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| advanced ovarian cancer patient | Experimental | Procedure: buccal cells, Procedure: bone marrow cells, Procedure: peripheral blood cells, Procedure: bone marrow biopsyWomen with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Women with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy.
Key exclusion criteria (2 listed)
- Presence of blood cell count abnormalities before PARP inhibitor treatment;
- Bone marrow infiltration by EOC cells.
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 |
|---|---|---|
| buccal cellscustom myeloid gene panel (Myelo-Panel) to identify germline mutations predisposing to cancer development (Thermo Fisher Scientific) | Procedure or surgery | advanced ovarian cancer patient |
| bone marrow cellsBone marrow cells (optional, for comparison, only in a limited number of patients): * morphological analysis * immunophenotype * cytogenetics/FISH * analysis of CHIP by custom gene panel and high sensitivity NGS | Procedure or surgery | advanced ovarian cancer patient |
| peripheral blood cellsanalysis of CHIP by custom gene panel and high sensitivity NGS | Procedure or surgery | advanced ovarian cancer patient |
| bone marrow biopsyBone marrow biopsy (optional, for comparison, only in a limited number of patients): * histology * immunohistochemistry | Procedure or surgery | advanced ovarian cancer patient |
Primary outcome
Identification of the events and determination of their incidence in study patient's population:
Time frame: 8 years
The study is descriptive in nature and no formal statistical testing is necessary or applicable. * Cell blood count abnormalities * Morphological alterations allowing a diagnosis of myelodysplastic syndrome or acute myeloid leukemia * Chromosomal abnormalities * Clonal hematopoiesis and extent of the expansion and evolution of the CHIP clones induced by PARP inhibitors. One of the primary objectives is to estimate the proportion of patients with stable abnormalities in hematologic counts. A patient is defined as having stable abnormalities in hematologic counts if the status "CTCAE grade ≥ 2 and/or platelets <100,000/mmc" persists for at least two weeks.The 90% confidence interval of the proportion of patients with stable abnormalities in hematologic counts will be calculated using the exact one-sided binomial test.
1 secondary outcome
Survival data evaluation
Time frame: 8 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2025.
- 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.
Federica Gigli principal investigator
Istituto Europeo di Oncologia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing buccal cells, bone marrow cells and peripheral blood cells in people with Leukemia, Myeloid, Acute and Myeloid Dysplasia, run by European Institute of Oncology at 1 site in Italy.
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 1 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 20 Jan 2025. 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Federica Gigli (+390257489538, federica.gigli@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of the events and determination of their incidence in study patient's population: (time frame: 8 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jan 2025.