Clinical Research Directory

Study of Cell-free DNA in Children and Adolescents With Acute Lymphoblastic Leukemia

Minimal residual disease (MRD) monitoring is a key prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Currently, MRD assessment relies mainly on cellular DNA obtained from bone marrow aspirates. Although highly informative, this approach has limitations, including the need for invasive procedures and the fact that it reflects only the bone marrow compartment. Tumor cells release fragments of genomic DNA into the bloodstream, known as circulating cell-free DNA (cfDNA). In solid tumors, cfDNA analysis has emerged as a valuable non-invasive biomarker for disease monitoring and treatment response. Recent studies have shown that cfDNA is detectable in pediatric ALL. This study aims to investigate whether plasma cfDNA analysis could represent an alternative or complementary approach to bone marrow-based MRD assessment. cfDNA may better reflect the global tumor burden across the entire body and allow more frequent longitudinal monitoring during treatment. The primary objective is to assess the correlation between MRD measured in plasma cfDNA and MRD measured in bone marrow cellular DNA at two key timepoints of treatment: the end of induction (Day 29) and the end of consolidation (Day 71-78). Secondary objectives include evaluating the correlation between peripheral blood cellular DNA and bone marrow MRD, describing clonal evolution using cfDNA throughout treatment and follow-up, exploring the concordance of genomic alterations detected in cfDNA and other biological compartments, assessing the prognostic value of cfDNA MRD for relapse risk and event-free survival, and characterizing cfDNA fragmentome and methylome signatures in patients compared with healthy controls. The study will include children and adolescents with newly diagnosed ALL treated at two AP-HP pediatric hematology centers, as well as a control cohort of healthy children undergoing HLA typing for sibling stem cell transplant.

Tracjectories and Predictors of Chemotherapy Induced Peripheral Neuropathy in Children With Acute Lymphoblastic Leukemia

The goal of this study is to explore the trajectory patterns of chemotherapy induced peripheral neuropathy over the course of chemotherapy and identify predictors of distinct trajectories in children with acute lymphoblastic leukemia. A perspective longitudinal study design is utilized. Chemotherapy induced peripheral neuropathy was assessed at one week after the first use of Vincristine (VCR) (T1), one week after the second use of VCR (T2), one week after the third use of VCR (T3), one week after the fourth use of VCR (T4), two weeks after T4 (T5), two weeks after T5 (T6), two weeks after T5 (T7). Patients' demographic and clinical characteristics, physical symptoms, nutrition status, psychological distress, sleep quality, physical activity, perceived social support and coping strategy are obtained at baseline.

Children's Laughter and Fun Yoga as Adjunctive Pain Relief Following Chemotherapy.

The goal of this clinical trial is to learn if a home-based program that combines laughter and fun yoga can help lower pain in children receiving chemotherapy. The study focuses on children with acute lymphoblastic leukemia who experience pain during treatment with chemotherapy and steroids. The main questions this study aims to answer are: 1. Does adding laughter and fun yoga to usual care lower pain levels in children receiving chemotherapy? 2. Does this program reduce the need for strong pain medicines, such as opioids? 3. Does the program help improve mood, anxiety, and sleep during treatment? Researchers will compare children who receive laughter and fun yoga plus usual care with children who receive usual care alone to see if the program works. Participants will: 1. Be randomly assigned to either the laughter and fun yoga group or the usual care group 2. Take part in the study during a 6-day period after receiving their chemotherapy treatment 3. Have their pain measured once each day using a child-friendly pain scale 4. Have parents answer short questions about pain medicine use, mood, anxiety, and sleep The laughter and fun yoga activities are gentle, safe, and designed to be done at home with the help of a parent. All participants will continue to receive their regular medical care throughout the study.

Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL

This research study is evaluating a drug called ribociclib (LEE011) given in combination with everolimus and other standard of care chemotherapy drugs as a possible treatment for relapsed or refractory ALL. The names of the drugs involved in this study are: * ribociclib * everolimus * dexamethasone

Newly-diagnosed Low Risk Pediatric B-cell ALL Protocol

CCCG-ALL2025 LR-B-ALL plan is designed based on the CCCG-ALL2020 plan. This is a clinical trial using 14 days of blinatumomab (Blina-14) as early intensification after induction therapy and 2nd Blina-14 in consolidation therapy in all newly diagnosed provisional low-risk (LR) pediatric acute lymphoblastic leukemia (ALL) patients, regardless of measurable residual diseases (MRD) status. We will compare the efficacy of chemotherapy combined with Blina-14, comparing to CAT+ intensification or historical regimens. Patients with early remission in depth will receive chemo-light late intensification and maintenance therapy afterwards. Early complete remission in depth and maintenance reduction will be determined by next-generation sequencing (Ig-NGS MRD).

Role of SF3B1 Mutation in Assessment of Acute and Chronic Lymphatic Leukemia

aim of the work 1. To evaluate the presence of SF3B1-K700E mutation in acute lymphoblastic leukemia and chronic lymphocytic leukemia. 2. To determine the correlation between the presence of SF3B1-K700E mutation with other laboratory findings.

Online Physical Activity and Health Counseling for Survivors of Childhood Acute Lymphoblastic Leukemia

Advances in the medical treatment of childhood acute lymphoblastic leukemia (ALL) have resulted in 5-year survival rates above 90%- however, the success is not without consequences. Childhood ALL survivors experience markedly impaired physical capacity - reducing their opportunity to engage in everyday activities including leisure activities, sports, and school - affecting their quality of life. Furthermore, Childhood ALL survivors have markedly increased risk of chronic medical conditions including cardiometabolic diseases - that can be prevented through an active lifestyle. Thus, it is imperative to develop novel interventions that can mitigate these treatment-related late-effects. In this RCT, including 82 childhood ALL survivors (10-21 years-old), we will investigate a 26-week online exercise intervention combined with access to a lifestyle physical activity webpage, and health consultations on cardiorespiratory fitness (primary outcome) markers of metabolic syndrome, and physical activity habits. While other pilot studies have investigated the effects of exercise for childhood ALL survivors, this study is the first RCT internationally to investigate the effects of online exercise combined with education through an app and health counselling for childhood ALL survivor. Using this approach, we are geographically able to reach every survivor in our targeted population, thereby, minimizing logistic challenges like travel distances. This study has the potential to radically change the way physical rehabilitation is approached in childhood ALL survivors - Potentially changing the workflow of health professionals from referring only survivors with specific deficits to local physiotherapy to referring all survivors to an exercise program tailored to their needs. By improving the children's general physical capacity, we can give the children the required tools to re-enter everyday life activities, including school physical education, leisure activities, and sports earlier after treatment has ended - ultimately minimizing the social complications of treatment. This study will also answer the government´s call to digitalize 30% of rehabilitation by the 2030.

Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

The study is a monocentric, interventional study that evaluates the efficacy of allogeneic HLA-matched or haploidentical transplantation consisting of an irradiation-based conditioning regimen coupled with donor Treg/Tcon adoptive immunotherapy for high-risk acute leukemia patients.

Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol

Building upon the results from the CCCG-ALL-2015, CCCG-ALL-2020 multicenter study cohort, concurrent research findings, and the latest clinical trials, the CCCG-ALL-2025 I/HR-B-ALL is thus developed to further improve the event-free survival (EFS), and overall survival (OS), and quality of life (QoL) of children with intermediate- and high- risk B-cell childhood acute lymphoblastic leukaemia (I/HR-B-ALL), while decreasing adverse reactions and transplantation rates. This trial primarily aims to explore: 1. The efficacy of two randomized Blinatumomab application scheme on I/HR-ALL as determined by MRD negatvitiy rate. 2. The efficacy of modified mini-hyperCVD + Venetoclax in I/HR-ALL cannot afford blinatumomab, in contrast to historical control as determined by MRD negatvitiy rate.

Psychiatric Problems in Children With Acute Lymphoblastic Leukemia and Their Caregivers

Cancer in childhood represents a significant health challenge, with approximately 400,000 children and adolescents aged 0-19 years diagnosed annually. The oncological landscape of pediatric populations is characterized by diverse malignancies, with leukemias, brain cancers, lymphomas, and solid tumors such as neuroblastoma and Wilms tumors constituting the predominant diagnostic categories. Among these, acute lymphoblastic leukemia (ALL) emerges as the most prevalent childhood malignancy. Historically, a cancer diagnosis portended an almost invariably fatal outcome. However, contemporary medical interventions have dramatically transformed this narrative. Since 1980, mortality rates across pediatric cancer types have declined by more than 50%, representing a remarkable advancement in clinical oncology. Notably, ALL demonstrates an exceptionally optimistic prognosis, with over 90% of patients achieving complete remission. Despite these encouraging survival statistics, the cancer experience extends beyond physiological parameters. Children diagnosed with leukemia and their familial support systems frequently encounter complex psychological challenges. These manifestations encompass a spectrum of emotional responses, including anxiety, shock, denial, depression, and adaptive difficulties. Critically, these psychological sequelae are not confined to the diagnostic and treatment phases but often persist even after disease remission The multidimensional nature of the cancer experience prompted the emergence of a specialized subdiscipline in 1992. Termed "psycho-oncology" in the United States and "psychosocial oncology" predominantly in European contexts, this field addresses two fundamental psychological dimensions: Emotional and psychosocial responses of patients, families, and caregivers throughout the disease trajectory Psychological, behavioral, and social factors potentially influencing cancer morbidity and mortality. Consequently, contemporary pediatric oncological care adopts a holistic paradigm. The therapeutic objective transcends mere physical restoration, aspiring to ensure the comprehensive social and emotional well-being of both the child and the familial ecosystem.

An Extension Study to Evaluate the Safety and Efficacy of an Anti-CD19 CAR-T Product in Patients with B-cell Lymphoproliferative Disorders

This follow-up study is designed to evaluate the long-term safety and effectiveness of a treatment called anti-CD19 CAR-T cell therapy in adults with certain B-cell blood cancers. These cancers include types that have returned after treatment or have not responded to other therapies. CAR-T cell therapy involves using a patient's own immune cells, which are modified in a lab to specifically target and destroy cancer cells with a marker called CD19. The study will look at how well patients tolerate this treatment over time, as well as its ability to keep cancer in remission or reduce its severity. Patients who have previously received CAR-T therapy in an earlier clinical trial and meet specific criteria can participate in this study. The research will include regular follow-up visits over approximately 11 months to monitor for side effects, assess cancer response, and track the activity of CAR-T cells in the body. This study does not involve additional treatments but focuses on understanding the long-term outcomes of CAR-T therapy to provide better care for patients in the future.

Autologous Hematopoietic Stem Cell Transplantation Combined With CD19-CART Treatment of Adult High-risk Acute Lymphoblastic Leukemia

To observe the efficacy and side effects of autologous hematopoietic stem cell transplantation combined with CD19-CART for adult acute lymphoblastic leukemia, and to evaluate the safety and efficacy of this regimen in the treatment of acute lymphoblastic leukemia.