Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

B-cell Lymphoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Acute Graft Versus Host Disease

All patients will be treated on this single arm

Autologous T cells activated and transduced with a chimeric antigen receptor targeting CD19

CD19 CAR T cells

Amos Toren, MD,Phd

Elad Jacoby, MD

Diana Bar

This phase 1 / 2 study will evaluate the response of B-cell malignancies expressing CD19 to autologous T cells transduced with a second generation anti-CD19 chimeric antigen receptor in children and young adults.

Autologous T cells transduced with chimeric antigen receptors (CAR) that recognize the CD19 antigen (CD19-CAR T cells) have been used in multiple clinical trials at several institutions worldwide. We established an in-house manufacturing process for CD19-CAR T cells with a CD28 (cluster of differentiation 28) costimulatory domain.

Primary Objectives:

1. To study the safety of administration of CAR T cell at the Sheba Medical Center
2. To determine the feasibility and efficacy of administering anti-CD19-CAR T cells in children and young adults with B cell malignancies.

Secondary Objectives

1. To study in vivo and in vitro behavior of CAR T cell in patients, including persistence, expansion, cytotoxic potential and exhaustion.
2. To study the cytokine milieu in CAR treated patients.

Eligibility Patients 1-50 years of age, with a CD19-expressing B-cell malignancy that has recurred after, or not responded to, one or more standard chemotherapy-containing regimens.

Design Peripheral blood mononuclear cells (PBMCs)will be obtained by leukapheresis. Anti-CD19 CAR T cells will be manufactured from fresh autologous PBMCs. PBMC will be cultured in the presence of anti-CD3 (cluster of differentiation 3) antibody and interleukin-2 followed by retroviral vector supernatant containing the anti-CD19 CAR. Total culture time is between 7-10 days. Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion, and on day 0 will receive one million CAR T cells per kilogram. Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia; for response of their underlying malignancy; and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).

T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies

A Phase 1 / 2 Single Arm Study of T-cells Expressing Anti-CD19 Chimeric Antigen Receptor in Pediatric and Young Adult Patients With B-cell Malignancies

Overall response rate = complete response (CR) + partial response (PR) + complete response with incomplete count recovery (CRi) in leukemia patients; Assessment using bone marrow evaluation for patients with leukemia, and imaging (CT / PET CT) for patients with lymphoma

For each participant, the feasibility of generating sufficient autologous CAR T cells within 12 days will be evaluated.

Enumeration of CAR T cells in the blood and bone marrow of participants

Assessment of T cells from peripheral blood by flow cytometry for expression of activation and exhaustion markers.

Measurement of cytokines in the blood of participants following CAR T cell administration

Sheba Medical Center

Symptoms and General Pathology

Recurrence

Disease Attributes

CD19 CAR T cells will be intravenously infused to patient in a three-day split-dose regimen: 10% on day 0, 30% on day 1 and 60% on day 2.

CD19 CAR T cells was transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB.

Dehui Zou, Dr.

In this single-center, open-label, no control, prospective clinical trial, a total of 10 relapsed or refractory CD19 positive B-cell Non-Hodgkin Lymphoma (NHL) patients will be enrolled.CD19 CAR T cells(total dose of 2×10\^6/kg-1×10\^7/kg) will be intravenously infused to patient in a three-day split-dose regimen: 10% on day 0, 30% on day 1 and 60% on day 2. The purpose of current study is to determine the clinical efficacy and safety of CD19 CAR T cells in patients with relapsed or refractory CD19 positive B-cell lymphoma.

In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a total of 10 relapsed or refractory CD19+ B-cell Non-Hodgkin Lymphoma (NHL) patients will be enrolled. CD19 CAR T cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB, will be administered by i.v. injection in a three-day split-dose regimen: 10% on day 0, 30% on day 1 and 60% on day 2. Side effects of CD19 CAR T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19 CAR T cells therapy in patients with relapsed or refractory CD19 positive B-cell lymphoma.

CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma

Juventas Cell Therapy Ltd.

Institute of Hematology & Blood Diseases Hospital, China

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Chronic Lymphocytic Leukemia

Chronic Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Antipyretics

Analgesics

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Acetaminophen

Diphenhydramine

Promethazine

Leukopharesis: cells collected with a target of ≥1 x10\^9 TNC with ≥3% CD3+ cells.

Lymphodepleting chemotherapy: 4 days of IV chemotherapy with fludarabine and cyclophosphamide.

* Fludarabine 30 mg/m2/day IV x 4 days (days -6 through -3)
* Cyclophosphamide 500 mg/m2/day IV x 2 days (days -6 and-5)

anti-CD19 CAR T cells:

* 0.3 - 1 x 10\^6 per kilogram for patients \<50 kg
* Flat dose of 0.3 - 1 x 10\^8 for patients ≥50 kg

The cell infusion will take place on day 0 (at least 2 days after completion of lymphodepleting chemotherapy). The patient will receive pre-medication with acetaminophen and diphenhydramine 30-60 minutes prior to the cell infusion.

Infusion of CD19 CAR-T Cells manufactured on-site using the CliniMACS Prodigy

CD19 specific Chimeric Antigen Receptor T Cell

Clelie Peck

Margaret Lamb, MD

This pilot study examines the safety and efficacy of anti-CD19 CAR T cells manufactured on-site in children and young adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.

Patients will undergo screening, leukapheresis (cell collection), lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the anti-CD19 CAR T cell infusion. The lymphodepleting chemotherapy is administered over four days IV to prepare the body for the CAR T cells. The anti-CD19 CAR-T cells are infused between 2-14 days after the last dose of chemotherapy. This study is designed for participants to begin lymphodepleting chemotherapy during the CAR T cell manufacture and receive a fresh cell infusion on the day that manufacturing is complete. Some patients may need more time in between the cell collection and the CAR T cell infusion, therefore, the cells may be manufactured and frozen prior to administration. Patients will be followed for a year after the cell infusion on the study and for up to 15 years to monitor for potential long term side effects of cell therapy.

PRIMARY OBJECTIVE:

* To examine the feasibility of manufacture and administration of autologous CD19 CAR T cells at a minimum target dose of 0.3 x 10\^6 to 1 x 10\^6 per kilogram for patients \<50 kg and a flat dose of 0.3 - 1 x 10\^8 for patients ≥50 kg using the Miltenyi CliniMACS Prodigy automated T Cell Transduction (TCT) process.
* To evaluate the safety of administration of CD19 CAR T cells after lymphodepletion with fludarabine and cyclophosphamide.

SECONDARY OBJECTIVE:

• To estimate the efficacy of CD19 specific CAR-T cells in pediatric and young adult patients with relapsed/refractory CD19+ B-cell ALL and NHL.

EXPLORATORY OBJECTIVE:

• To evaluate the persistence of CD19 CAR T cells after infusion.

The autologous lymphocytes are collected from the patient via apheresis. The apheresis product is then transported to the on-site GMP facility for manufacture of the CAR T cell product. Patients may be admitted to begin lymphodepleting chemotherapy during the CAR T cell manufacturing process. When the CAR T cell product is ready, the cells may be administered fresh or may be cryopreserved for use at a later date depending on the patient's clinical status.

All patients will be admitted to the hospital to undergo a Fludarabine/Cyclophosphamide based leukoreduction conditioning regimen to be completed 2-14 days prior to CAR T cell infusion. Patients will be admitted for a minimum of 7 days after the CAR T infusion to monitor for toxicity including cytokine release syndrome, neurologic toxicity, and tumor lysis syndrome.

Lymphodepleting chemotherapy:

* Fludarabine 30 mg/m2/day IV x 4 days
* Cyclophosphamide 500 mg/m2/day IV x 2 days

CD19 CAR T cell dose:

* 0.3 x 10\^6 to 1 x 10\^6 per kilogram for patients \<50 kg
* Flat dose of 0.3 - 1 x 10\^8 for patients ≥50 kg

A single-arm, unblinded, pilot treatment study

Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL

Safety and Feasibility of On-Site Manufacture of CD19 CAR T Cells Using the CliniMACS Prodigy in Pediatric and Young Adult Patients With Relapsed/Refractory CD19 Positive Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

Reported as the proportion of products successfully manufactured and infused

Proportion of patients achieving a response at 1 month post infusion

Complete response rate at 1 month post infusion

Best overall response (complete response, partial response, stable disease, progressive disease)

MRD status at 30 days post infusion will be presented with descriptive statistics. MRD will be performed utilizing both flow cytometry and NGS.

Overall survival and event free survival will be assessed using the Kaplan-Meier method. Survival will be measured as the time from cell infusion to event or censoring.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies	NCT02772198	Acute Lymphobla... Non-Hodgkin Lym...	CD19 CAR T cell...	1 Year - 50 Years	Sheba Medical Center
CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma	NCT03029338	Lymphomas Non-H... Relapse	CD19 CAR T cell...	18 Years - 70 Years	Institute of Hematology & Blood Diseases Hospital, China
CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma	NCT03029338	Lymphomas Non-H... Relapse	CD19 CAR T cell...	18 Years - 70 Years	Institute of Hematology & Blood Diseases Hospital, China
CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma	NCT03029338	Lymphomas Non-H... Relapse	CD19 CAR T cell...	18 Years - 70 Years	Institute of Hematology & Blood Diseases Hospital, China
Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL	NCT05779930	Acute Lymphobla... Non-Hodgkin's L... Non-Hodgkin's L... Acute Lymphobla... B-cell Non Hodg... B Cell Leukemia	CD19 specific C...	- 30 Years	Nationwide Children's Hospital
T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies	NCT02772198	Acute Lymphobla... Non-Hodgkin Lym...	CD19 CAR T cell...	1 Year - 50 Years	Sheba Medical Center
Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL	NCT05779930	Acute Lymphobla... Non-Hodgkin's L... Non-Hodgkin's L... Acute Lymphobla... B-cell Non Hodg... B Cell Leukemia	CD19 specific C...	- 30 Years	Nationwide Children's Hospital
Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed/Refractory CD19 Positive ALL and NHL	NCT05779930	Acute Lymphobla... Non-Hodgkin's L... Non-Hodgkin's L... Acute Lymphobla... B-cell Non Hodg... B Cell Leukemia	CD19 specific C...	- 30 Years	Nationwide Children's Hospital

Spots Global Cancer Trial Database for cd19 car t cells