Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Frailty

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

Individual biological aging determined by DNA methylation analysis will be assessed at D0, M3 and M12.

An optional bone marrow sample will be taken during the myelogram performed at diagnosis.

Individual fragility and quality of life will be assessed using geriatric tools at D0, M6, M12, M24 and M36

Blood and bone marrow sample

Lise LACLAUTRE

Mélanie CASILE, PhD

Anne PARRY, MD

Gabriel ETIENNE, MD

Atchroue JOHNSON ANSAH, MD

Marc BERGER, Pr

Melanie CASILE, PhD

Eric HERMET, MD

Clément LAHAYE, MD

Lydia ROY, MD

Vanessa PANTE, Dr

Vanessa PANTE, MD

Valérie COITEUX, MD

Amélie PENOT, MD

Jean Baptiste FARGEAS, MD

Aude CHARBONNIER, MD

Gabrielle ROTH-GUEPI, MD

Jean-Yves NIEMIER, MD

Laurence LEGROS, MD

Emanuelle DURON, MD

Martine ESCOFFRE-BARBE, MD

Philippe RENAUDIER, MD

Blandine DELAVIGERIE, MD

Françoise HUGUET, MD

Clément GAUDIN, MD

Philippe ROUSSELOT, Pr

Marc BERGER

French prospective multicenter, open-label study involving newly diagnosed CML patients. Two assessments will be performed during the follow-up of these patients: individual frailty using geriatric tools and individual biological aging determined by DNA methylation analysis.

Value of Biological Age, in Addition to Individual Frailty, for Personalising the Management of Cancer Treated With Targeted Therapy

Value of Biological Age, in Addition to Individual Frailty, for Personalising the Management of Cancer Treated With Targeted Therapy: the Model of Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

The difference between biological age and chronological age (of the clone and the patient) expressed as a difference and as a percentage.

Individual fragility assessed by Geriatric Core Data set assessing social status, independence at home, mobility, nutrition, cognitive status, mood and comorbidities.

Individual fragility assessed by Rockwood clinical frailty score ranging from 1 (very fit) to 9 (at the end of life)

Tolerance assessed by actual dose received

Tolerance assessed by the number of tyrosine kinase inhibitor discontinuation due to intolerance

Tolerance assessed by a description of adverse events as assessed by CTCAE v5.0

Tolerance assessed by changes and number of tyrosine kinase inhibitor lines

Tolerance assessed by a description of treatment sequences

Individual fragility assessed by Geriatric Core Data set assessing social status, independence at home, mobility, nutrition, cognitive status, mood and comorbidities at the time of diagnosis.

Individual fragility assessed by Rockwood clinical frailty score ranging from 1 (very fit) to 9 (at the end of life) at the time of diagnosis.

Quantification of BCR::ABL transcript expressed as copy number relative to 100 copies of control gene transcripts

Decrease in residual disease and achievement of MMR (≤0.1%), MR4 (≤0.01%), MR4.5 (≤0.032%), MR5 (≤0.001%) thresholds)

Quality of life assessed using the European Organisation for Research and Treatment of Cancer LG Core Questionnaire (EORTC QLQ-C30) is a 30-item instrument designed to measure quality of life in all cancer patients, with a higher score indicating a better health-related quality of life

University Hospital, Clermont-Ferrand

Shock

Vaccines

Heat Shock Protein 70 HSP70

Zihai Li, MD,Ph.D.

Description: The trial is designed to determine the response of the immune system of patients with CML to a vaccine made from their own tumor. Researchers believe that this particular vaccine, which is made from purified heat shock proteins taken from each patient's tumor, alerts the body's immune system to recognize and attack invading cancer. To be considered potentially eligible for this study you must have CML in the chronic phase.

Length/Duration: Vaccinations will be administered weekly for eight weeks. One clinic follow up visit will be scheduled two weeks after the final vaccination.

Rational for immunotherapy of CML

Conceptually,CML in chronic phase is the best model for immunological intervention. It is a disease as a result of chromosomal translocation, which generates a true tumor-specific antigen. Patients in chronic phase have relatively preserved immune function for a prolonged period of time. Studies have indeed shown that peptides spanning the junctional region of both the bcr/abl and abl/bcr fusion proteins can bind to major histocompatibility complex (MHC) class I molecules (Berke et al. 2000). Vaccination of patients with bcr/abl breakpoint fusion peptides generates specific immune responses (Pinilla-Ibarz et al. 2000). In addition, for patients relapsed after bone marrow or stem cell transplant, donor lymphocyte infusion is effective in inducing a majority of them into remission. The role of donor lymphocyte infusion has proven the original concept of graft versus leukemia effect and the effectiveness of immunotherapy, in practice, towards CML (Dazzi et al. 1999). More recently, it was found that the presence of cytotoxic T lymphocytes (CTL) against HLA-A2-restricted myeloid-specific antigen proteinase 3 correlates significantly with cytogenetic remission of CML treated either with IFN or stem cell transplant (Molldrem et al. 2000), which provides strong evidence for a role of T cell immunity in clearing malignant cells.

Current proposal and hypothesis:

Based on the established roles of HSPs in T cell immunity and a large body of preclinical and clinical safety data, we propose to initiate a pilot study to test the feasibility of immunization with autologous tumor-derived HSP70 in the treatment of CML in chronic phase. This study will facilitate more clinical trials in the future, testing the ultimate hypothesis that the combination of the cytostatic therapy such as IFN and STI571, with specific immunomodulator such as HSP70 offers the best chance of eradication of CML. A total of 10 eligible patients will be enrolled in the study. All eligible patients will undergo aphaeresis to collect peripheral blood mononuclear cells. The autologous HSP70 is then purified using the standard protocol. After passing the established sterility testing, the patients are immunized intradermally with 50 micrograms HSP70 for a total of 8 injections in 2 months. They may receive their standard therapy during this time. In addition to collecting the feasibility and toxicity data, the development of anti-tumor immunity will be measured by,

1. an increase in peripheral blood of IFN-gamma producing CD8+ T-lymphocytes which are reactive to the autologous bcr/abl positive peripheral mononuclear cells
2. an increase of PR-1 specific CTLs by PR1-HLA-A2 tetramer techniques in patients who are HLA-A2 positive
3. the change of immunophenotype of peripheral lymphocytes
4. the cytogenetic remission of Philadelphia chromosome from the bone marrow

Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase

A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase

University of Connecticut

Heart and Blood Diseases

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Behaviors and Mental Disorders

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasm Metastasis

Ovarian Neoplasms

Hematologic Neoplasms

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Sarcopenia

Neoplasms, Second Primary

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Breast Neoplasms

Lung Neoplasms

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Rectal Neoplasms

Kidney Neoplasms

Atrophy

Muscular Atrophy

Neuromuscular Manifestations

Neurologic Manifestations

Pathological Conditions, Anatomical

Neoplastic Processes

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urogenital Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Quality of Life

Ovarian Cancer

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Standard follow-up MNA, IPAQ, SARC-F and SarQOL questionnaire

Standard follow-up with clinical exams, functionnal test at baseline, Ct scan MNA, IPAQ, SARC-F and SarQOL questionnaires

Standard

Magali BALAVOINE

Katell LE DU, MD

Julien DOMONT, MD

Sarcopenia is defined as reduction in muscle mass and function according to the criteria of the European Working Group on Sarcopenia in older people. Initially described for elderly patients, it is also presented as a negative prognostic factor in overall survival in oncology in certain locations (lung, ENT pathways, colon, pancreas) and more controversially for hemopathies. Its screening by measurement of skeletal muscle mass by CT scan and / or PET scan against L3 and by physical functional tests is not routinely integrated despite international recommendations. Sarcopenia is one of the characteristics of patient fragility that can induce more complications, lengthen the average length of hospital stay and reduce overall survival. The PRONOPALL score, a predictor score for survival validated by a previous study, will be correlated with the presence (or absence) of sarcopenia at inclusion for patients with a solid tumor (breast, ovary, prostate cancer , kidney, lungs, pancreas, colorectal). A prospective study on 38 patients with metastatic cancer was carried out at the Victor Hugo clinic in Le Mans between 01/JUN/21 and 31/AUG/21 (SPACE, ClinicalTrials.gov number, NCT04714203): 25 patients were analyzable on the CT and PRONOPALL score data with a prevalence of sarcopenia of 60% and median overall survival of 14 months (unpublished data), clinical performance and muscle strength tests were not carried out (as in the publications cited above).

A prospective study for the detection of sarcopenia is indicated by extending to blood diseases with the integration of clinical tests included in the initial APA (Adapted physical activity) assessment recommended for diagnosis.

Assessment of Sarcopenia at Diagnosis for Patients With Previously Untreated Metastatic Cancer or Hematologic Malignancy

Assessment of the Proportion of Patients With Sarcopenia at Diagnosis for Patients With Previously Untreated Metastatic Cancer or Hematologic Malignancy.

Sarcopenia is defined for those under 60 years of age by LMSI\<43.1 cm²/m² for men and \<32.7 cm²/m² for women, and for patients over 60 years of age by \<38.6 cm²/m² for men and \<30.7 cm²/m² for women..

Calculated from the date of inclusion to the date of death due to any cause or the date last known to be alive if patient is censored.

Calculated from the date of start of treatment to the date of first event (progression, death, infectious complications, thrombosis, side effects of treatments of grade 2 or higher)

Calculated from the date of start of treatment to the date of first progression of disease based on Investigator assessment or the date of death or censored at the date of the last valid tumor assessment before start of a new therapy for patients who are still alive and without progression

Calculated from the date of start of treatment for all unplanned hospitalizations for side effects of treatments of grade 2 or higher, infectious complications, thrombosis, relapse or progression

For the cancer subtypes concerned (breast, colon, rectum, lungs, ovaries, prostate, kidney, pancreas)

Calculated according to WHO classification

Calculated from the number of patients who were screened for sarcopenia at diagnosis in the active file of patients meeting the inclusion criteria in all participating centers

Weprom

Antineoplastic Agents

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Asciminib

Nilotinib

Dasatinib

Imatinib Mesylate

Niacinamide

Niacin

Nicotinic Acids

Protein Kinase Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Trace Elements

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Asciminib 80mg taken orally once a day starting cycle 1 day 1 for up to 24 months during the single agent asciminib phase.

Patients who have not achieved MR4.5 after 24 months will be given a low dose tyrosine kinase inhibitor (low-TKI). There will be three options of low-TKIs to be given at the investigator's discretion.

Potent tyrosine kinase inhibitor that displays anti-tumor activity by specifically targeting the ABL myristate-binding pocket (STAMP).

For subjects that do not achieve MR4.5 (molecular response) after 24 months of single-agent asciminib will be offered the addition of nilotinib 300mg, once daily, with the goal of attaining MR4.5.

Ascimininb + Nilotinib

For subjects that do not achieve MR4.5 (molecular response) after 24 months of single-agent asciminib will be offered the addition of imatinib 300mg, once daily, with the goal of attaining MR4.5.

Asciminib + Imatinib

For subjects that do not achieve MR4.5 (molecular response) after 24 months of single-agent asciminib will be offered the addition of dasatinib 50mg, once daily, with the goal of attaining MR4.5.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Value of Biological Age, in Addition to Individual Frailty, for Personalising the Management of Cancer Treated With Targeted Therapy	NCT06130787	Leukemia,Myeloi...	Blood and bone ...	18 Years -	University Hospital, Clermont-Ferrand
Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase	NCT00027144	Leukemia,Myeloi... Leukemia,Myeloi...	Heat Shock Prot...	18 Years -	UConn Health
Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase	NCT00027144	Leukemia,Myeloi... Leukemia,Myeloi...	Heat Shock Prot...	18 Years -	UConn Health
Assessment of Sarcopenia at Diagnosis for Patients With Previously Untreated Metastatic Cancer or Hematologic Malignancy	NCT05154474	Metastatic Canc... Cancer, Breast Cancer Colon Cancer, Rectum Cancer, Lung Cancer Ovaries Cancer Prostate Cancer, Kidney Cancer Pancreas Myeloma Myelodysplasia Leukemia, Myelo... Leukemia,Myeloi... Leukemia, Lymph... Leukemia, Lymph...	Standard	18 Years -	Weprom
Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase	NCT05143840	Chronic Myeloid... Adult CML Leukemia, Myelo... Leukemia,Myeloi...	Asciminib Ascimininb + Ni... Asciminib + Ima... Asciminib + Das...	18 Years -	Augusta University
Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase	NCT05143840	Chronic Myeloid... Adult CML Leukemia, Myelo... Leukemia,Myeloi...	Asciminib Ascimininb + Ni... Asciminib + Ima... Asciminib + Das...	18 Years -	Augusta University

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