Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Docetaxel

Epirubicin

Aromatase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Dalpiciclib: Take 125 mg once daily for 3 weeks, then stop for 1 week. Each cycle is completed in 4 weeks.

AI: Take according to the instructions provided.

Docetaxel for injection: Administered as a 75 mg/m2 intravenous infusion Epirubicin hydrochloride for injection: Administered as a 75 mg/m2 intravenous infusion.

Cyclophosphamide for injection: Administered as a 500 mg/m2 intravenous infusion.

Dalpiciclib: Take 125 mg once daily for 3 weeks, then stop for 1 week. Each cycle is completed in 4 weeks. It is recommended to take the medication approximately at the same time each day, with warm water, preferably on an empty stomach. Fasting for at least 1 hour before and after medication is advised.

Dalpiciclib

AI: Take according to the instructions provided.

Aromatase inhibitor

Administered as a 75 mg/m2 intravenous infusion over approximately 30 minutes. It is given every three weeks and dose reduction or treatment delay is allowed, up to a maximum delay of 3 weeks from the previous dose calculation. Treatment will be terminated if the delay exceeds this limit.

Docetaxel injection

Administered as a 75 mg/m2 intravenous infusion. It is given every three weeks and dose reduction or treatment delay is allowed, up to a maximum delay of 3 weeks from the previous dose calculation. Treatment will be terminated if the delay exceeds this limit.

Epirubicin Hydrochloride Injection

Administered as a 500 mg/m2 intravenous infusion. It is given every three weeks and dose reduction or treatment delay is allowed, up to a maximum delay of 3 weeks from the previous dose calculation. Treatment will be terminated if the delay exceeds this limit.

Cyclophosphamide injection

lina zhang

Cuizhi Geng, M.D.

This study is a multi-center, randomized, prospective phase II clinical trial aimed at exploring and evaluating the efficacy of dalpiciclib combined with AI in neoadjuvant treatment for ER strong positive（ER≥50%），HER2-negative, Ki-67≤20%,T1-3N1M0 postmenopausal breast cancer. The primary objectives are to demonstrate non-inferiority in efficacy compared to chemotherapy and to assess its superior safety profile.

This study is a multi-center, randomized, prospective non-inferiority exploratory phase II clinical trial. Eligible subjects were randomly assigned in a 1:1 ratio to either the dalpiciclib combined with AI group （neoadjuvant endocrine group） or the AC-T group （chemotherapy group） after screening. The administration of the investigational drugs started within 48 hours after randomization. Subjects will receive either 24 weeks of dalpiciclib combined with AI or AC-T treatment until disease progression, intolerable adverse events, withdrawal of informed consent, or discontinuation by the investigator's judgment.

Dalpiciclib Plus AI (Neoadjuvant Endocrine Therapy) Compared With Neoadjuvant Chemotherapy in Early Breast Cancer （EBC）

A Phase II Randomized, Non-inferiority Study Comparing the Efficacy and Safety of Dalpiciclib Combined With AI With Neoadjuvant Chemotherapy in ER+ HER2- Postmenopausal Breast Cancer Patients

Radiological response is the percentage of participants with CR or, PR according to RECIST v.1.1. A responder is defined as any participant who exhibits a CR or PR. CR is the disappearance of all target lesions. PR is a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. PD is 20% increase in the sum of diameters of target lesions taking as reference the smallest sum and the appearance of 1 or more new lesions.

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, emotional, cognitive, or social functioning), global health status and symptom scales of fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.

Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. 6 variables are included in a calculation formula.

PEPI stands for Preoperative Endocrine Prognostic Index. It is a scoring system used in breast cancer research to assess the response to neoadjuvant endocrine therapy. PEPI evaluates various factors, including tumor size, lymph node involvement, Ki-67 proliferation index, and estrogen receptor status, to predict the risk of recurrence and overall prognosis in patients with hormone receptor-positive breast cancer. The PEPI score helps in determining the effectiveness of neoadjuvant endocrine therapy and guiding treatment decisions.

pCR is defined as absence of invasive cancer in the breast and sampled regional lymph nodes.

Tumor tissue collected through a core biopsy at baseline and at the end of cycle 1 was used to determine Ki67 expression. Ki67 expression is defined as the percent of cells staining positive by validated central assay.

The toxicity will be evaluated according to the scale CTC-AE version 5.0

Hebei Medical University Fourth Hospital

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

B-cell Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Fludarabine

Fludarabine phosphate

Dimethoate

1.5 x 10\^6 transduced T cells/kg (± 20%)

500 mg/m2 IV over 30-60 minutes +/- 10 minutes before Fludarabine Days -5, -4, - 3

30 mg/m2 IV over 30-60 minutes +/- 10 minutes after cyclo- phosphamide infusion Days -5, 4, -3

Fludarabine Injection

Cells are to be infused intravenously (IV) over 30 minutes or less via nonfiltered tubing either by gravity or a peristaltic pump, gently agitating the bag during infusion to prevent cell clumping

CD19-CD34t metabolically programmed CAR transduced T-cells

Alan Brisendine

Jasmin Brooks

Alan Brisendine, CCRP

Brian Hess, MD

Brian Hess, PHD

This is a single-center, nonrandomized, open-label dose-escalation study followed by dose-expansion of CD19- CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Although CD19 CAR T-cell therapy is a dynamic scientific and clinical breakthrough for CD19+ NHL, issues still remain in terms of relapse, toxicity, and availability. This trial will incorporate a CD34 tag (CD34t) into the CAR T-cell construct, thus allowing a more purified CAR T-cell product via CD34 selection. This purification step will hopefully lead to an improvement in safety/toxicity. Furthermore, the issue of CD19 CAR T-cell relapse has been linked to a lack of CAR T-cell fitness. With the knowledge that Th1 T-cell subsets have improved effector function and Th17 T-cell subsets have improved persistence, the investigators plan to expose the collected T-cells to priming conditions that lead to a metabolically enhanced CAR-T cell product akin to a Th1/17 hybrid cell. The investigators hypothesize that these metabolically programmed CD19 CAR-T cells will yield a high- quality product with enhanced persistence and anti-tumor efficacy when purified based on CD34t expression.

Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL

A Phase 1b Dose Escalation Study of Metabolically Fit CD19 Chimeric Antigen Receptor (CAR) T Cells With CD34 Selection Markers in Adult Patients With Relapsed or Refractory CD19 B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Maximum tolerated dose (MTD), maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of CD19-CD34t metabolically programmed CAR T-cells

Rate of grade 3 or higher cytokine release syndrome(CRS)

rate of grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS)

1. Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL based on overall response rate (ORR) and complete remission (CR) rate. The response rate for patients with NHL will be determined by the 2014 Lugano IWG criteria. The response rate for CLL/SLL patients will be determined by the 2018 iwCLL criteria

Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL based on progression free survival (PFS), duration of response (DOR), and overall survival (OS)

Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL treated at the RP2D based on ORR and CR rate. The response rate for patients with NHL will be determined by the 2014 Lugano IWG criteria. The response rate for CLL/SLL patients will be determined by the 2018 iwCLL criteria

Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL treated at the RP2D based on PFS, DOR and OS.

Safety of CD19-CD34t metabolically programmed CAR T-cells at the RP2D, including all grade incidence of CRS and ICANS

Medical University of South Carolina

Assistant Professor

Syndrome

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Graft vs Host Disease

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Homologous Wasting Disease

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Calcineurin Inhibitors

Matched sibling transplants will receive PTCy + ATG2.5 ± ATG1.5

Unrelated transplants will receive PTCy + ATG5.0

ATG 5.0

Cyclophosphamide 50 mg/kg on days +3 and +4

ATG 2.5 mg/kg on day -1 ± 1.5 mg/kg on day -2

ATG 2.5±1.5

Leonardo J Arcuri, MD, PhD

Hematopoietic stem cell transplantation is a curative treatment for a number of benign and malignant hematologic diseases. One of the key parts of hematopoietic stem cell transplantation is the prophylaxis of graft-versus-host disease. Since the end of the 1970s, with the introduction of cyclosporine, calcineurin inhibitors (cyclosporine and tacrolimus) have become part of almost all prophylactic regimens, even though they are a group of drugs with a poor toxicity profile that requires monitoring. constant serum level. Since 2008, post-transplant cyclophosphamide has been introduced with great success, associated with a calcineurin inhibitor and mycophenolate, in the prophylaxis of graft-versus-host disease in haploidentical transplantation (50% matched).

Since then, in view of this enormous success, efforts have been made to incorporate post-transplant cyclophosphamide in matched related and unrelated transplants, or with a mismatch.

This is a prospective, 2-arm, non-randomized study. Arm 1, with related donors, and arm 2, with unrelated donors. Patients will be allocated in these arms according to donor availability (patients with a matched-sibling donor will receive a matched-sibling transplant; patients with no related donors but with unrelated donors, an unrelated transplant).

Patients who are ready for transplantation with matched-sibling or unrelated donors will be recruited to participate in the study.

The stem cell collection target will be 5E6 CD34/kg recipient weight for peripheral source. If a quantity greater than this is collected, the remainder will be cryopreserved according to the institutional protocol.

Graft-versus-host disease prophylaxis will be performed on D+3 and D+4 with cyclophosphamide and with ATG on D-1 or on D-2 and D-1, depending on ATG de-escalation, for matched-sibling transplants, according to prespecified criteria based on the 3+3 approach; and on D+3 and D+4 with cyclophosphamide and with ATG on D-2 and D-1, for unrelated donors.

Patients with a matched sibling donor will be assigned to the PTCy+ATG2.5±1.5 arm, while patients with an matched unrelated donor will be assigned to the PTCy+ATG5.0 arm

PTCy and ATG for MSD and MUD Transplants

Efficacy Evaluation of Post-transplant Cyclophosphamide-based Graft-versus-host Disease Prophylaxis With ATG, Calcineurin Inhibitor-free, for Matched-sibling or Matched-unrelated Transplantation

Upon finalization of the study, data will be shared on reasonable requests.

Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria

Cumulative incidence of acute graft-versus-host disease, grades II-IV by the MAGIC criteria

Cumulative incidence of steroid-refractory graft-versus-host disease

Cumulative incidence of chronic graft-versus-host disease

Cumulative incidence of steroid-requiring chronic graft versus host disease

Cumulative incidence of death not caused by primary malignant disease or following relapse

Cumulative incidence of relapse of primary malignant disease

Composite outcome of death or primary disease relapse

Incidence of cytomegalovirus reactivation

Incidence of posttransplant lymphoproliferative disorder

Cumulative incidence of cytomegalovirus disease

Instituto Nacional de Cancer, Brazil

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Topotecan

Melphalan

Cyclosporine

Cyclosporins

Mycophenolic Acid

Tacrolimus

Busulfan

Thiotepa

Antilymphocyte Serum

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Clotrimazole

Miconazole

Antifungal Agents

Antitubercular Agents

Topoisomerase I Inhibitors

Folinic Acid

Folate

Vitamin B9

There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).

2.5 mg/kg/day；2 doses on day -3 and day -2 for matched sibling donor transplantation；3 doses on day -4，-3 and day -2 for unrelated donor transplantation；4 doses on day -5，-4，-3 and day -2 for haploidentical donor transplantation

Anti Thymocyte Globulin

60 mg/kg/day for 2 days in cord blood stem cell transplantation

2mg/m2/day for 3 days in cord blood stem cell transplantation

70mg/m2/day，for peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation；2 doses on day -3 and day -2 when conditioning regimen containing thiotepa；3 doses on day -4，-3 and day -2 when conditioning regimen not containing thiotepa；

5 mg/kg/day for 2 days in peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation

0.8mg/kg/dose；8 doses in cord blood stem cell transplantation；12 doses in peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation when conditioning regimen containing thiotepa；16 doses in peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation when conditioning regimen not containing thiotepa；

2.5\~4 mg/kg/dose every 12 hours orally；1.5\~2 mg /kg/dose every 12 hours intravenously; trough concentration maintained at 150\~250ng/ml

0.02\~0.03 mg/kg/day as continuous infusion or 12 hour divided doses

Mycophenolate Mofetil

15 mg/m2/dose on d+1 and 10 mg/m2/dose on d+3，d+6 in peripheral stem cell transplantation

Ke Huang, MD

Su Liu, MD

Yang Li, MD

Jianpei Fang, MD

Yang Li

Jianpei Fang

Neuroblastoma (NB) is the most common extracranial solid tumor of embryonal origin in children. According to the International Neuroblastoma Risk Group (INRG) staging criteria and the International Neuroblastoma Staging System (INSS) ，NB preoperative staging is divided into L1, L2, M and Ms stages, the postoperative staging is divided into 1 to 4 stages and 4s stage. Among them, 4/M stage is of the highest degree of malignancy and the worst prognosis. Despite the aggressive combination therapy, the 5-year survival rate (OS) is still less than 15%, and the 2-year relapse rate is 80%. Currently, no effective treatment is accessible for refractory/relapsed stage 4/M NB after completing conventional therapy.

In hematopoietic stem cell transplantation (HSCT) , conditioning regimen with high-dose radiotherapy and chemotherapy is implemented to eradicate tumor cells and abnormal clonal cells in the patient, block the pathogenesis, and restore the patient's hematopoietic and immune systems by transplanting normal hematopoietic stem cells. According to the source of hematopoietic stem cells, HSCT can be divided into two types: autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been confirmed that benefiting from the graft versus tumor(GVT) effect, allo-HSCT can clear residual lesions in refractory/relapsed NB patients post-auto-HSCT，and prolong the survival time of patients. Our center has explored the conditioning regimen, treatment of residual tumor lesions before transplantation, and strategies to reduce transplantation-related death (TRM) and enhance the GVT effect. However, the sample size is small, and multicenter and larger sample size research are needed. This study will further observe the clinical efficacy and safety of allo-HSCT in the treatment of 4/M stage NB, and provide a new treatment method and option for 4/M stage NB.

Purposes: To evaluate the efficacy and safety of allo-HSCT in children with stage 4/M high-risk NB through a multi-center prospective single-arm clinical research grouped according to different types of donors, graft sources, and stratified conditioning regimen.

Primary objectives: To evaluate the efficacy (3-year OS, EFS) of allo-HSCT in the treatment of children with stage 4/M NB through a multicenter prospective single-arm clinical study.

Secondary objectives:

1. To evaluate the safety of allo-HSCT in the treatment of children with stage 4/M NB \[toxicity of conditioning regimen, engraftment rate, early transplantation-related mortality (\<100d TRM), transplantation-related complications (VOD, thrombotic microangiopathy(TMA), acute/chronic graft-versus-host disease (GVHD), Epstein-Barr virus(EBV)/cytomegalovirus(CMV) viremia and EBV/CMV related diseases or other pathogenic infections, etc.\];
2. Improvement and optimization of allo-HSCT conditioning regimen. Outline: This is a multicenter study. Conditioning regimen: There are 3 protocols according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+cyclophosphamide (CTX)+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).

Transplantation: Patients undergo cord blood stem cell or bone marrow or granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cell transplantation on day 0.

GVHD prophylaxis: Cyclosporine or tacrolimus combined with methotrexate is used for related matched transplantation, cyclosporine combined with mycophenolate mofetil for umbilical cord blood transplantation, and cyclosporine combined with mycophenolate mofetil and methotrexate for haploidentical transplantation to prevent GVHD.

After completion of transplantation, patients are followed periodically at least 3 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dalpiciclib Plus AI (Neoadjuvant Endocrine Therapy) Compared With Neoadjuvant Chemotherapy in Early Breast Cancer （EBC）	NCT06107673	Breast Cancer	Dalpiciclib Aromatase inhib... Docetaxel injec... Epirubicin Hydr... Cyclophosphamid...	18 Years - 75 Years	Hebei Medical University Fourth Hospital
Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL	NCT05702853	B-cell Non Hodg... Chronic Lymphoc...	Cyclophosphamid... Fludarabine Inj... CD19-CD34t meta...	18 Years -	Medical University of South Carolina
PTCy and ATG for MSD and MUD Transplants	NCT06299462	Acute Myeloid L... Acute Lymphobla... Myelodysplastic... Hodgkin Lymphom... Non-hodgkin Lym...	ATG 5.0 Cyclophosphamid... ATG 2.5±1.5	18 Years - 60 Years	Instituto Nacional de Cancer, Brazil
Dalpiciclib Plus AI (Neoadjuvant Endocrine Therapy) Compared With Neoadjuvant Chemotherapy in Early Breast Cancer （EBC）	NCT06107673	Breast Cancer	Dalpiciclib Aromatase inhib... Docetaxel injec... Epirubicin Hydr... Cyclophosphamid...	18 Years - 75 Years	Hebei Medical University Fourth Hospital
Allogeneic Hematopoietic Stem Cell Transplantation for 4/M Neuroblastoma	NCT05303727	Neuroblastoma	Anti Thymocyte ... Fludarabine Cyclophosphamid... Topotecan Melphalan Thiotepa Busulfan Cyclosporine Tacrolimus Mycophenolate M... Methotrexate	- 18 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
PTCy and ATG for MSD and MUD Transplants	NCT06299462	Acute Myeloid L... Acute Lymphobla... Myelodysplastic... Hodgkin Lymphom... Non-hodgkin Lym...	ATG 5.0 Cyclophosphamid... ATG 2.5±1.5	18 Years - 60 Years	Instituto Nacional de Cancer, Brazil

Spots Global Cancer Trial Database for cyclophosphamide injection