CAR-T Therapy in Relapsed or Refractory Haematopoietic and Lymphoid Malignancies

This is an open, single-arm, phase I clinical study to evaluate efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) in the treatment of hematopoietic and lymphoid malignancies. A total of 30 patients are planned to be enrolled over a period of 2 years.

Study Overview

• Status: Unknown
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Biological: Autologous CAR-T

Detailed Description

Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30, CD7, BCMA, CD123, etc. may be potential in developing the corresponding CAR-T cells to treat patients whose tumors expressing those markers. Investigators have developed a high efficient platform for constructing different CARs and preclinical studies have demonstrated effective killing of corresponding target cells. In this study, investigators will evaluate their safety and efficacy in patients with different types of hematopoietic and lymphoid malignancies. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • Hematology Department, Hebei Medical University Fourth Hospital
      • Contact: Lihong Liu, PhD & MD; Phone Number: +8613831177920; Email: limmune@gmail.com
      • Principal Investigator: Lihong Liu, PhD & MD
      • Contact: PhD & MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1.The treat history meeting the following criteria:

1. Recurrence of lymphoma patients with imaging (CT/MRI/PET-CT) detection and pathological diagnosis, or recurrence including bone marrow morphology relapse and the MRD recurrence of myeloma patients or leukemia patients, after chemotherapy or stem cell transplantation;
2. Can't get complete remission (including MRD positive) after more than twice repeated chemotherapy of incipient lymphoma, myeloma or leukemia patients;
3. One or twice chemotherapy cannot get remission again (including MRD positive), but not suitable for chemotherapy of incipient lymphoma, myeloma or leukemia patients.

2. There is a measurable lesions before treatment at least; 3. ECOG score≤2; 4. To be aged 1 to 70 years; 5. More than a month lifetime from the consent signing date

Exclusion Criteria:

1. Serious cardiac insufficiency, left ventricular ejection fraction<50;
2. Has a history of severe pulmonary function damaging;
3. Merging other malignant tumor;
4. Merging uncontrolled infection;
5. Merging the metabolic diseases (except diabetes);
6. Merging severe autoimmune diseases or immunodeficiency disease;
7. patients with active hepatitis B or hepatitis C;
8. patients with HIV infection;
9. Has a history of serious allergies on Biological products (including antibiotics);
10. Happened in 3 ~ 4 acute GvHD after allogeneic hematopoietic stem cell transplantation on recurring patients
11. Pregnancy or lactation women;
12. Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation.

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: Autologous CAR-T cells; Patients will be be treated with autologous CAR-T cells.	Biological: Autologous CAR-T; Patients will be drawn 50-100 ml blood to obtain enough peripheral blood mononuclear cells (PBMC) for CAR-T manufacturing. The T cells will be purified from the PBMC, transduced with CAR lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CAR-T cells will be infused.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor load	Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR T cell persistence	CAR T cell persistence will be quantified with flow cytometry and qPCR	Up to 24 months]

Collaborators and Investigators

• Sponsor: Hebei Senlang Biotechnology Inc., Ltd.
• Collaborators: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Lihong Liu, PhD & MD, Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 23, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2016040

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No