Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Patients whose diagnosis met the histological criteria of PMLBL according WHO classification with a diagnosis of CNS involvement at relapse/progression

Andres Ferreri

Stefania Trinca

Andrés Jose Maria Ferreri, MD

Teresa Calimeri, MD

retrospective study focused on patients with a known diagnosis of PMLBCL which experienced a CNS relapse during the course of their disease to obtain information about the clinical characteristics, the management at diagnosis and at each relapses , and the outcome of these cases. The aim of the study is to put together the large International series on CNS+ PMLBCL data, coming from 6 different countries , on clinical factors, anti-lymphoma therapy administered alone or concomitant with CNS prophylaxis , the information about the site of re biopsy when available , the dose intensity of lymphoma therapy received at relapse and the outcome of patients.

Both patients treated in routine practice or within clinical trials will be considered. Moreover to better characterized the pathological features of this rare entity a central pathological review of the initial diagnosis and when available of for histological confirmed relapse will be considered.

Primary Mediastinal Large B-cell Lymphoma With CNS Involvement

Retrospective Multicenter International Study on Prognostic Factors, Management And Outcome Of Primary Mediastinal Large B-Cell Lymphoma (PMLBCL) Patients With Central Nervous System (CNS) Involvement

to describe the PMLBCL characteristics at diagnosis and at CNS relapse ( first relapse or second and subsequent recurrences) and the treatment received to describe the median time to CNS relapse to define prognostic factors of outcome of CNS relapse in PMLBCL patients

to correlate treatment strategy with survival end-points

to evaluate the Progression Free Survical ( PFS) after CNS events

to evaluate Overall Survival ( OS) after CNS relapse to centra! pathological reviewed the initial diagnosis and the relapse and to correlate biological and molecular factors with CNS recurrence

IRCCS San Raffaele

Lymphoma Unit Director

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Subjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JCAR017 cells infusion. Phase 1 will evaluate up to 5 JCAR017 cells dose levels and dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. The declared RP2D in Phase 1 will be applied to the subjects enrolled in Phase 2

JCAR017

Lymphodepleting

Bristol-Myers Squibb

This is a Phase 1/2, open-label, single arm, multicohort study to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL.

Phase 1 will identify a recommended Phase 2 dose (RP2D). Phase 2 will evaluate the efficacy of JCAR017 RP2D in the following three disease cohorts: Cohort 1 (r/r B-ALL), Cohort 2 (MRD+ B-ALL) and Cohort 3 (r/r B-NHL, \[DLBCL, BL, or PMBCL\]). A Simon's Optimal two-stage study design will be applied to Cohort 1 and 2 in Phase 2.

This is a Phase 1/2, open-label, single arm, multicohort study incorporating Simon's Optimal two-stage design to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL.

In the Phase 1, up to 5 dose levels will be of JCAR017 will be evaluated. Enrollment will commence in pediatric subjects with r/r B-ALL at Dose Level 1 (DL1) of 0.05x10\^6 CAR+ T cells/kg (maximum DL1 of 5x10\^6 JCAR017 CAR+ T cells \[non-weight adjusted\]). If this dose is confirmed to be safe and tolerable, additional subjects will be enrolled at higher dose(s) up to 0.75 x10\^6 CAR+ T cells/kg (maximum of 75x10\^6 JCAR017 CAR+ T cells \[non-weight adjusted\]) with the aim to identify the RP2D. Dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. A Safety Review Committee (SRC) will recommend the Phase 2 dose (defined as RP2D) based on an integrated assessment of the safety, PK and preliminary efficacy information from at least 10 pediatric subjects treated at the RP2D.

In Phase 2, a minimum of 71 additional subjects (\< 18 years of age) will be enrolled into one of the 3 cohorts listed below. The sample size for Cohorts 1 and 2 is calculated according to Simon's Optimal two-stage design. The 10 or more pediatric subjects treated at the RP2D in Phase 1 will form part of the sample size (ie, Cohort 1 and Cohort 2). Therefore, the protocol intends to treat 81 primary endpoint evaluable pediatric subjects in Phase 2, if warranted by the evaluation of results at the completion of the first stage of the study in each cohort.

* Cohort 1 (r/r B-ALL): 48 evaluable pediatric subjects (13 subjects in Stage 1 and 35 in Stage 2)
* Cohort 2 (MRD+ B-ALL): 23 evaluable pediatric subjects (9 subjects in Stage 1 and 14 subjects in Stage 2)
* Cohort 3 (r/r B-NHL \[DLBCL, BL, or PMBCL\]): 10 evaluable pediatric subjects. Due to the very low incidence rate and therefore expected low subject accrual, there is no formal sample size for this arm.

Up to 20 additional B-ALL subjects between 18 and 25 years of age may be enrolled in Phase 2.

Following treatment with JCAR017 subjects will then enter the post-treatment period for disease progression/relapse, safety, CAR T cell persistence, and survival up to 24 months after administration of JCAR017.

Efficacy will be assessed both locally and by an Independent Review Committee. Response assessments will be based on bone marrow and blood morphologic criteria, physical examination findings, along with laboratory assessments of cerebral spinal fluid (CSF) and bone marrow MRD (B-ALL only) assessments. B-NHL subjects will also have radiographic disease assessment by CT/MRI scans and tumor biopsies, if accessible.

Post-study follow-up for survival, relapse, long-term toxicity, and lentiviral vector safety will continue under a separate long-term follow-up protocol for up to 15 years after the JCAR017 infusion as per health authority regulatory guidelines.

An Independent Data Monitoring Committee will monitor the study conduct.

A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)

A Phase 1/2, Open-label, Single Arm, Multicohort, Multicenter Trial to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL).

The dose recommended for use in phase 2 studies on the basis of dose limiting toxicities observed in phase 1 studies.

Total number of subjects achieving a Complete response (CR) or CR with incomplete blood count recovery (CRi) on Day 28 and confirmed on Day 56 as determined by IRC assessment.

Total number of subjects achieving a CR or CRi with an MRD negative bone marrow (\<0.01% tumor cells) on Day 28 and confirmed on Day 56 as determined by IRC assessment.

Total number of subjects achieving a CR or PR on Day 28 as determined by IRC assessment.

Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups)

Percentage of r/r B-ALL subjects achieving a best overall response (BOR) of CR or CRi on Day 28, confirmed on Day 56 as determined by IRC assessment

Time from first response until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first

Time from JCAR017 infusion to documentation of PD, disease relapse, or death due to any cause, whichever occurs first

Time from JCAR017 infusion to PD, disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first

Time from JCAR017 infusion to time of death due to any cause

Number of B-ALL subjects achieving CR or CRi and a negative MRD bone marrow.

Percentage of subjects who achieve a response after JCAR017 infusion and then proceed to HSCT

Number of r/r B-NHL subjects achieving BOR of CR/PR

Celgene

Symptoms and General Pathology

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

CG-806 will be given orally in ascending doses in patients with relapsed or refractory CLL/SLL or Non-Hodgkin's Lymphomas (escalation cohort), until the maximum tolerated dose or recommended dose is reached. Followed by up to 100 patients enrolled in the expansion cohort at the recommended dose.

CG-806 will be given orally in ascending doses starting at 150 mg PO BID until the maximum tolerated dose or recommended dose is reached.

CG-806

Rafael Bejar, MD, PhD

This study is being done to evaluate the safety, tolerability and effectiveness of Oral CG-806 for the treatment of patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or Non-Hodgkin's Lymphomas who have failed or are intolerant to two or more lines of established therapy or for whom no other treatment options are available.

This is a multicenter, open-label, Phase Ia/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory CLL/SLL or Non-Hodgkin's Lymphoma patients. This is to be followed by a cohort expansion phase at the MTD or recommended oral dose.

A Study of CG-806 in Patients With Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas

A Phase Ia/b Trial to Evaluate the Safety and Tolerability of CG-806 in Patients With CLL/SLL or Non-Hodgkin's Lymphomas

To determine the safety and tolerability of CG-806.

To determine the dose of CG-806 given orally every 12 hours that maintains a biologically active plasma concentration over a period of 28 days.

To establish the recommended Phase 2 dose (RP2D) of CG-806 for future clinical trials in patients with advanced CLL/SLL or NHL.

Pharmacokinetic variables including maximum plasma concentration (Cmax)

Pharmacokinetic variables including minimum plasma concentration (Cmin)

Pharmacokinetic variables including Area Under the Curve (AUC)

Pharmacokinetic variables including volume of distribution

Pharmacokinetic variables including clearance

Pharmacokinetic variables including serum half-life

To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluations

Pharmacodynamic biomarkers of drug effect including BTK activity

Pharmacodynamic biomarkers of drug effect including selected mRNA levels

To assess the relative bioavailability of original formulation (G1) against new generation formulation (G2).

To assess the relative bioavailability of original formulation (G1) against new generation formulation (G3).

Aptose Biosciences Inc.

Cicatrix

Universal CD19-specific CAR gene-engineered T cells

Lung-Ji Chang, Ph.D

The purpose of this study is to assess the feasibility, safety and efficacy of universal CAR T cell therapy against CD19-positive hematological malignancies using a novel CD19-specific CAR T cell product, 4SCAR19U T cells. The study also aims to learn more about the function of the 4SCAR19U T cells and their persistence in patients. This is a phase I trial enrolling patients from multiple clinical centers.

Chimeric antigen receptor (CAR) T cell therapy has proven effective in treating B cell malignancies. However, the application itself is still limited by the high cost and long preparation time which often do not meet the urgent need of patients. In addition, some patients may suffer from long-term immunosuppression caused by tumor microenvironment or after radiotherapy and chemotherapy, resulting in exhaustion, aging and functional defects of the autologous T cells, which will eventually affect the quality of the CAR-T cells and affect the clinical efficacy.

The 4SCAR19U T cells are genetically engineered and manufactured in bulk amount that can be supplied off-the-shelf without being custom made from individual patients. The immediate availability of the CAR-T cells makes clinical treatment convenient and timely for rapid progressing disease or for the highly immune suppressed patients. This application can be time- and cost-effective. This novel approach may also overcome problems of functionally defective autologous T cells. The purpose of this clinical trial is to assess the feasibility, safety and efficacy of the 4SCAR19U T cell product in hematological malignancies. Another goal of the study is to learn more about the function of this novel product and its persistence in the patients

4SCAR19U T Cells Targeting B Cell Malignancies

Universal 4SCAR19U T Cell Therapy for the Treatment of Relapsed and Refractory B Cell Malignancies

Safety of 4SCAR19U T cells in patients with relapsed and refractory B-ALL, BCL using CTCAE 4 standard to evaluate the level of adverse events

Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Primary Mediastinal Large B-cell Lymphoma With CNS Involvement	NCT06024694	Primary Mediast...		18 Years - 80 Years	IRCCS San Raffaele
Primary Mediastinal Large B-cell Lymphoma With CNS Involvement	NCT06024694	Primary Mediast...		18 Years - 80 Years	IRCCS San Raffaele
A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)	NCT03743246	Precursor Cell ... Lymphoma, Non-H...	JCAR017 Lymphodepleting Fludarabine Cyclophosphamid...	- 25 Years	Celgene
A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)	NCT03743246	Precursor Cell ... Lymphoma, Non-H...	JCAR017 Lymphodepleting Fludarabine Cyclophosphamid...	- 25 Years	Celgene
A Study of CG-806 in Patients With Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas	NCT03893682	Chronic Lymphoc... Small Lymphocyt... Non-Hodgkin's L...	CG-806	18 Years -	Aptose Biosciences Inc.
4SCAR19U T Cells Targeting B Cell Malignancies	NCT05995015	B Cell Malignan...	Universal CD19-...	6 Months - 75 Years	Shenzhen Geno-Immune Medical Institute
A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)	NCT03743246	Precursor Cell ... Lymphoma, Non-H...	JCAR017 Lymphodepleting Fludarabine Cyclophosphamid...	- 25 Years	Celgene

Spots Global Cancer Trial Database for pmbcl

Every month we try and update this database with for pmbcl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pmbcl

Every month we try and update this database with for pmbcl cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pmbcl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.