Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Venetoclax

Azacitidine

Antimetabolites

Enzyme Inhibitors

Therapeutic outcomes in adults with Ph- B-ALL have substantially improved in the last decade, with complete remission (CR) and long-term overall survival (OS) rates of around 90% and 40%-50%, respectively. The presence of measurable residual disease (MRD) is the strongest predictor of relapse in B-ALL. In this study, high risk Ph- B-ALL patients receive the induction chemotherapy with Azacitidine+Venetoclax. After induction chemotherapy with Azacitidine+Venetoclax (VA regime), each subject receives CD19CD22 CAR-T cells by intravenous infusion. The patients with MRD negative will undergo HSCT.

Azacitidine Injection 75mg/square meter/day, day1-7, subcutaneous injection

Azacitidine Injection

Venetoclax 100mg day 1, 200mg day 2, 400mg d3-d21, oral

After induction chemotherapy with Azacitidine+Venetoclax, each subject receives CD19CD22 CAR-T cells by intravenous infusion

CD19CD22 CAR-T

xiaowen Tang, phD

Depei Wu, PhD

Clinical trial for the safety and efficacy of induction chemotherapy with VA regime and bridging CD19CD22 CAR-T therapy in adult patients with newly diagnosed high-risk and Ph- B-ALL

To evaluate the safety and efficacy of induction chemotherapy with VA regime and bridging CD19CD22 CAR-T therapy in Adult patients with newly diagnosed high-risk and Ph- B-ALL in this prospective, single arm study.

CD19CD22 CAR-T Therapy in Patients With High-Risk B Acute Lymphoblastic Leukemia (B-ALL).

Clinical Trial for the Safety and Efficacy of Induction Chemotherapy With Azacitidine+Venetoclax (VA) and Bridging CD19CD22 CAR-T Therapy in Adult Patients With Newly Diagnosed High-Risk and Ph-negative (Ph-) B-ALL

MRD Negative Remission Rate after CD19CD22 cell therapy

Complete Molecular Remission Rate after CD19CD22 CAR-T cell therapy

From the first infusion of CD19CD22 cells to death or the last visit

Up to 2 years after CD19CD22 CAR-T cells infusion

The First Affiliated Hospital of Soochow University

Nutritional and Metabolic Diseases

Hyperglycemia

Childhood Acute Lymphoblastic Leukemia

Hypoglycemic Agents

Gastrointestinal Agents

Insulin

Insulin, Globin Zinc

Asparaginase

Pancrelipase

Pancreatin

Insulin, Short-Acting

Subjects will receive insulin via hybrid closed-loop insulin delivery system during the chemotherapy phases that contains steroid and asparaginase. This treatment will be initiated within 4 days of starting induction chemotherapy treatment.

Participants will utilize the Tandem Control-IQ Professional Hybrid Closed Loop artificial pancreas system \[25, 26\]. This device consists of the Dexcom G6 Continuous glucose monitor (or a more recent interoperable CGM), the Tandem t:slim X2 continuous subcutaneous insulin infusion pump, and the Control-IQ professional hybrid closed loop control algorithm. The CGM is generally replaced by parents or patients and then replaced after sensor expiration or if it falls off. This CGM, like all future iCGMs, is factory calibrated and approved for direct dosing of insulin. In addition, while the system is in use, patients will conduct blood glucose level checks at least four times a day with a fingerstick and calibrate the CGM if the measurements differ by more than 20 mg/dL of fingerstick blood glucose level. The t:slim X2 insulin pump delivers rapid acting insulin via a subcutaneous cannula which is placed by parents or patients and then replaced every 3 days \[30\].

Hybrid Closed Loop System

Gregory Forlenza, MD

The overall objective of this pilot study is to determine the safety and feasibility of a hybrid closed-loop insulin delivery system for children and young adults with high risk acute lymphoblastic leukemia, during the induction chemotherapy phase while they are exposed to steroids and asparaginase that cause hyperglycemia.

The overall objective of this pilot study is to determine the safety and feasibility of a hybrid closed-loop insulin delivery system for children and young adults with high risk acute lymphoblastic leukemia, during the induction chemotherapy phase while they are exposed to steroids and asparaginase that cause hyperglycemia. Insulin therapy would be beneficial in reducing hyperglycemia-associated complications in this period and thereby could improve other outcomes. The primary objective of the current pilot proposal is to demonstrate that hybrid closed loop pump therapy is a safe to be used in children and young adults with high risk acute lymphoblastic leukemia. If successful, the results of this study will be used to plan and support a larger, multi-center clinical trial and a grant proposal.

This is a non-randomized prospective cohort study about the safety and feasibility of a commercially available hybrid closed loop insulin delivery system in children and young adults with high-risk ALL who are at high risk of hyperglycemia due to an intensive chemotherapy regimen containing steroids and asparaginase

HCL Single Arm Pilot Study in Treatment of Hyperglycemia of Pediatric ALL

Safety and Feasibility Study of a Hybrid Closed-loop Insulin Delivery System for Children and Young Adults With High Risk Acute Lymphoblastic Leukemia

The primary outcome measures for this study will be the safety of HCL insulin delivery by hypoglycemia exposure. One of the primary endpoints is CGM Time in hypoglycemia (defined as blood glucose \< 70 mg/dL).

The primary outcome measures for this study will be the safety of HCL insulin delivery by hypoglycemia exposure. One of the primary endpoints is the number of episodes of symptomatic hypoglycemia. At each study visit, subjects will be asked about symptoms, such as shakiness, dizziness, blurred/impaired vision, sweating, pallor, clumsiness, difficulty paying attention, tingling around the lips, tongue or cheeks, change in mental status, or seizure.

Rate of infection at the CGM insertion site, measured in occurrences per patient-day.

Rate of bleeding at the CGM insertion site, measured in occurrence per patient-day.

Rate of infection at the HCL insulin infusion site, measured in occurrence per patient-day.

Rate of bleeding at the HCL insulin infusion site, measured in occurrence per patient-day.

Time in Ranges (TIRs) refers to percent of the time spent in a specific range of blood glucose levels, adding valuable information to assess the level of glycemic control. Usually a range of 70-180 mg/dL is used, but occasionally a more stringent 70-140 mg/dL is used. In this study, we will obtain %CGM TIRs in both ranges.

Mean glucose level will be obtained from CGM data to evaluate for glycemic variability

Rate of infection, length of hospitalization, length of PICU admission, rate of remission at the end of induction, and need for re-admission will be obtained as a part of clinical outcomes. These outcomes will be compared to a historical control group to investigate the effect size of relationships between glycemic control and clinical outcome. This exploratory aim will investigate correlations between glycemic control and outcomes to determine effect sizes for future studies and grant proposals.

Children's Hospital Colorado

DexCom, Inc.

Tandem Diabetes Care, Inc.

National Cancer Institute (NCI)

University of Colorado, Denver

Fludarabine

Fludarabine phosphate

Busulfan

Treosulfan

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses.

Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.

Blood samples (2x5ml EDTA tubes) should be collected just before the start of the conditioning regimen from every patient regardless of therapeutic arm by every centre and stored ≤-20°C Patient should be in remission (MRD negative) for this sampling, otherwise the sample should be taken using a mouth swab/saliva (not intravenously).

For second transplant patients, please provide DNA taken before first transplant or a fresh saliva samples.

Pharmacogenomics

Bu PK analysis after the first dose of IV Bu (+potential subsequent ones).

Blood sampling:

-\>For Bu 4 X/d: Before the first Bu dose (Time 0), then straight after the end of infusion (Time 1), then at 15 min (Time 2), 30 min (Time 3), 1 hour (Time 4) and 4 hour (Time 5) after the end of infusion

-\>For Bu 1 X/d: Before the first Bu dose (Time 0), then straight after the end of infusion (Time 1), then at 1 hour (Time 2), 3 hour (Time 3), 5 hour (Time 4), 7 hour (Time 5) and 11 hour (Time 6) after the end of infusion.

For centers not performing BU TDM, perform Dried Blood Sampling (DBS) analysis:

-\> 0.5ml blood sample should be collected and 5µl spotted onto DBS cards in duplicate. Dry them max 5 hours and then keep in a sealed envelope and store at -80°C, as below

Busulfan plasma level measurements

Marc Ansari, MD, PD

Patricia Huezo-Diaz Curtis, PhD

Nicolas Von der Weid

Marc Ansari

Güngör Tayfun

Christina Peters, Prof. MD PhD

Peter Bader, Prof. MD PhD

Franco Locatelli, Prof. MD PhD

Pharmacogenomics (PG) offers the opportunity to individualize treatment according to patient genetic variations which influence activity of enzyme metabolizing or acting in the pathway of prescribed chemotherapy drugs.

This add-on research aims to prospectively investigate variations in several candidate genes related to all types of chemotherapeutic drugs and TBI used in the main related study NCT 01949129, THE ALL SCTped FORUM study for their potential role as predictive biomarkers of PK variability and outcome of myeloablative therapy for pediatric patients receiving an allogeneic hematopoietic stem cell transplantation in acute lymphoblastic leukemia.

Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.

Busulfan (Bu) is a key compound in conditioning myeloablative regimens for patients undergoing hematopoietic stem cell transplantation (HSCT). Bu has been long used for the treatment of patients with leukemia and some congenital disorders; advantages and disadvantages of such treatment are well described. However, although Bu treatment has been shown to be effective, its use may be limited by related adverse events such as veno-occlusive disease (VOD), interstitial pneumonitis, acute Graft vs Host Disease (GVHD), and seizures. Thus, novel therapies are being investigated as well as the pharmacogenetics of these drugs. One of alternative drugs that may replace Bu due to its lower toxicity profile is Treosulfan (Treo). Fludarabine (Flu) is usually used in combination with Bu or Treo as an alternative to cyclophosphamide (Cy) also due to its lower toxicity. Thus, the Bu/Flu regimen is now being used more often than the previously more common Bu/Cy regimen. However, improvement to the regimen is still needed for reducing adverse drug effects. Pharmacogenomics (PG) offers the opportunity to individualize treatment according to patient genetic variations which influence activity of enzyme metabolizing or acting in the pathway of prescribed chemotherapy drugs.

This add-on research aims to prospectively investigate variations in several candidate genes (e.g GST, DCK and DNA repair pathway genes) related to all types of chemotherapeutic drugs (Bu/Flu/Thio; Treo/Flu/Thio and TBI/VP16) used in this protocol for their potential role as predictive biomarkers of pharmacokinetics (PK) variability and outcome of myeloablative therapy for pediatric patients receiving an allogeneic HSCT in acute lymphoblastic leukemia

For the busulfan arm countries: a cross-validation of busulfan quantification is performed. All Bu Therapeutic Drug Monitoring participating at the main ALL SCTped FORUM study will be assessed for the accuracy (%) and trueness (%) of 8 blinded Bu Quality Control samples. Criteria of acceptance are set according to FDA and ICH guidelines.

Blood samples will be collected prior to initiation of therapy for DNA banking and DNA analysis (for all patients), for DNA analysis (TBI/VP16, Bu/Flu/Thiotepa and Treo/Flu/Thiotepa groups) and PK analysis (only for the Bu group). PK and pharmacogenomic data will then be correlated with the studied outcomes (e.g.Veno-occlusive disease, Graft vs host disease, Treatment Related Mortality, Events Free Survival, Overall Survival).

Recruitment:

Patients (children) age 0-18 will be recruited in each arm. No oral Bu is allowed in this study.

Shipment (when there is a minimum of 10 patients) Send all the materials listed to: Dr Marc Ansari, Plateforme d'Hématologie et Oncologie Pédiatrique (CANSEARCH research laboratory), Faculté de Médecine, Bâtiment Tulipe, 5th floor, Av De La Roseraie 64, GENEVE 1205 Switzerland.

Contact Dr. Ansari's laboratory prior to shipment: Phone (+41 79 55 36 100) and e-mail (research@cansearch.ch). All shipments must be sent frozen by a carrier guaranteeing overnight delivery with the indication "Pharmacogenomic study" on the face of the parcel.

ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)

Allogeneic Stem Cell Transplant for Children and Adolescents With Acute Lymoblastic Leukemia FORUM - Pharmacogenomic Study (add-on Study)

Genotyping of candidates genes related to pharmacokinetics and pharmacodynamics of the studied agents.

Association study between the herein genetic variants and the below mentioned phenotypes (odd ratio).

defined as the first of 3 consecutive days with an absolute neutrophil count of 0.5x10\^9/L or higher

Defined as the first of 3 consecutive days with platelet counts higher that 20x10\^9/L without transfusion

Defined by persistent pancytopenia with no evidence of hematologic recovery of donor cells beyond 28 days after transplantation, and secondary graft failure by a rapid decrease in neutrophil count after successful engraftment

the time of transplant until all causes of death after transplant not related to relapse

the time of transplant until death, relapse or graft failure, whichever occurs first.

the time between transplantation and death due to any causes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CD19CD22 CAR-T Therapy in Patients With High-Risk B Acute Lymphoblastic Leukemia (B-ALL).	NCT06078306	B Acute Lymphob... Ph-Negative ALL High Risk Acute...	Azacitidine Inj... Venetoclax CD19CD22 CAR-T	18 Years - 65 Years	The First Affiliated Hospital of Soochow University
HCL Single Arm Pilot Study in Treatment of Hyperglycemia of Pediatric ALL	NCT05006040	High Risk Acute...	Hybrid Closed L...	10 Years - 26 Years	University of Colorado, Denver
ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)	NCT02670564	Acute Lymphobla...	Pharmacogenomic... Busulfan plasma...	- 18 Years	Swiss Pediatric Oncology Group
HCL Single Arm Pilot Study in Treatment of Hyperglycemia of Pediatric ALL	NCT05006040	High Risk Acute...	Hybrid Closed L...	10 Years - 26 Years	University of Colorado, Denver
CD19CD22 CAR-T Therapy in Patients With High-Risk B Acute Lymphoblastic Leukemia (B-ALL).	NCT06078306	B Acute Lymphob... Ph-Negative ALL High Risk Acute...	Azacitidine Inj... Venetoclax CD19CD22 CAR-T	18 Years - 65 Years	The First Affiliated Hospital of Soochow University
HCL Single Arm Pilot Study in Treatment of Hyperglycemia of Pediatric ALL	NCT05006040	High Risk Acute...	Hybrid Closed L...	10 Years - 26 Years	University of Colorado, Denver

Spots Global Cancer Trial Database for high risk acute lymphoblastic leukemia