Chimeric Antigen Receptor T Cells (CART) Therapy in Refractory/Relapsed B Cell Hematologic Malignancies

A Multicenter Efficacy and Safety Study of Cluster of Differentiation 19 (CD19)-Targeted CART (CD19CART) Therapy for CD19 Positive Relapsed or Refractory B-cell Hematologic Malignancies (SCT019-01）

This single arm, open-label, multi-center clinical trial is studying CD19 targeted chimeric antigen receptor T cells therapy in treating patients with CD19 positive malignant B-cell derived leukemia and lymphoma that is relapsed (after stem cell transplantation or chemotherapy) or refractory to chemotherapy.

Study Overview

• Status: Unknown
• Conditions: Lymphoma, B-Cell; Leukemia, B-Cell
• Intervention / Treatment: Biological: CD19CART

Detailed Description

This single arm, open-label, multi-center clinical trial is studying CD19 targeted chimeric antigen receptor T cells therapy in treating patients with CD19 positive malignant B-cell derived leukemia and lymphoma that is relapsed (after stem cell transplantation or chemotherapy) or refractory to chemotherapy. When patients enroll in this trial, autologous CD19CART cells were generated from the mononuclear cells of the patient's peripheral blood (PB). During the term of cell preparation of CD19CART cells, patients will receive a conditioning regimen. One day after completing conditioning regimen, the patient will be given infusions of CD19CART cells into the vein over a period of 1 to 3 days. Patients will be monitored for a response, toxic effects, and the expansion and persistence of circulating CD19CART cells.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Innovative Cellular Therapeutics CO., LTD.
    • Contact: Lei Xiao, Ph.D; Phone Number: +86-21-58950719
    • Principal Investigator: He Huang, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed as CD19 positive refractory and relapsed B cell hematologic malignancies included acute lymphoblastic leukemia (ALL),chronic lymphocytic leukemia(CLL),non-Hodgkin's lymphoma(NHL)
• not eligible or appropriate for auto-HSCT or allo-HSCT or relapsed after hematopoietic stem cell transplant(HSCT)
• At least one measurable lesion defined as one lesion larger than 1.5cm or two lesion more than 1.0cm(for patients with NHL )
• Age ≤60 years
• Eastern Cooperative Oncology Group(ECOG) Performance status 0 to 2, Expected survival > 6 months
• Left Ventricular Ejection Fraction (LVEF) > 50%
• no history of other malignancies;
• no other serious diseases which conflict with the treatment in the present trial
• All patients should consent to adopt efficient contraception methods during the treatment and after the treatment. The pregnant tests of women who are in child bearing period should be negative before the treatment.
• patients should understand and are willing to participate in the trial. Inform consent form is supposed to obtained before treatment

Exclusion Criteria:

• Diagnosis or classification undefined
• Those with primary central nervous system lymphoma or testicular leukaemia or lymphoma
• Patients with a known history or prior diagnosis of epilepsia or other disease affecting the central nervous system, or serious mental diseases;
• Patients who have secondary leukaemia or lymphoma after chemotherapy or radiotherapy for other malignancies
• Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy, concurrent use of immunosuppressant medications
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Pregnant or lactating women(the safety of this therapy on unborn children is not known)
• With active infection
• Active hepatitis B, hepatitis C or syphilis infection
• Patients use of systemic steroids within 2 weeks. Recent or current use of inhaled steroids is not exclusionary
• Prior treatment with gene therapy product
• Cluster of differentiation 3(CD3) positive cells<0.9x10^4/ml in peripheral blood (PB)
• Organ function meeting following criteria: liver and renal function: alanine aminotransferase(ALT)/aspartate aminotransferase(AST) > 3 times the upper limit of normal, or bilirubin>2.0 mg/dl（34.2umol/L）, or creatinine >2.5mg/dl（221.0umol/L） ; hematopoietic function:Neutrophil count<1.0x10^9/L，hemoglobin<80g/L，platelet <50x10^9/L(for patients with NHL )
• Any uncontrolled active medical disorder that would preclude participation as outlined
• HIV infection
• The researchers considered unsuitable to participate in this clinical study.
• Patients with poor compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm; Experimental: CD19 CART cell.The target dose range administered in this study is 1x10e5-1x10e7 CART-19 cells/kg.	Biological: CD19CART; Patients will be given infusions of CD19CART cells into the vein over a period of 1 to 3 days. The target dose range administered in this study is 1x10e5-1x10e7 CD19CART cells/kg. Patients will be monitored for a response, toxic effects, and the expansion and persistence of circulating CD19CART cells.; Other Names: CD19-directed chimeric antigen receptor modified T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of study related adverse events	up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Anti-leukemia or lymphoma responses to CD19CART cell infusions	up to 24 weeks

Collaborators and Investigators

• Sponsor: Innovative Cellular Therapeutics Co., Ltd.
• Investigators: Study Director: Yu Hu, Ph.D, Union Hospital,Tong Ji Medical College,Huazhong University of Science and Technology; Study Director: He Huang, Ph.D, The First Affiliated Hospital of the College of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: June 19, 2016
• First Submitted That Met QC Criteria: June 24, 2016
• First Posted (Estimate): June 27, 2016

Study Record Updates

• Last Update Posted (Estimate): June 28, 2016
• Last Update Submitted That Met QC Criteria: June 26, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: lymphoma; relapsed; refractory; leukemia; CD19+
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Neoplasms by Site; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Lymphoma; Lymphoma, B-Cell; Hematologic Neoplasms; Leukemia, B-Cell
• Other Study ID Numbers: SCT019-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED