Clinical Trial

Disease: Relapsed or Refractory B-Cell Malignancies, (NCT03398967)

Disease info:

B-cell malignancies are cancers that arise from abnormalities in B cells, and include B-cell lymphomas and leukaemias. While leukaemias typically originate in the bone marrow and spread through the bloodstream, lymphomas usually originate in the lymph nodes or the spleen and spread through the lymphatic system.

There are more than 70 known types of B-cell lymphoma, and these make up approximately 85 % of all cases of non-Hodgkin lymphomas in the United States. NHL is one of the most common cancers in the United States, accounting for about 4% of all cancers. B-cell lymphomas may grow and spread slowly with few symptoms (also known as indolent lymphoma) or may be very aggressive with severe symptoms. Other common types of B-cell lymphoma include:

  • Diffuse large B-cell lymphoma (DLBCL)
  • Follicular lymphoma
  • Chronic lymphocytic leukaemia (CLL) /small lymphocytic lymphoma (SLL)
  • Mantle cell lymphoma (MCL)
  • Marginal zone lymphomas
  • Burkitt lymphoma

In leukaemia, the bone marrow produces abnormal levels of white blood cells. B-cell acute lymphoblastic leukaemia (B-ALL) is an aggressive leukaemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the bone marrow and blood. B-ALL is the most common type of ALL. Note that B-ALL is also called B-cell acute lymphocytic leukaemia and precursor B-lymphoblastic leukaemia. 

Relapsed refers to when a patient has received active treatment, went off treatment and then the disease came back, whereas refractory refers to disease that is progressing despite active treatment.

 

Frequency:
NHL accounts for about 4% of all cancers in the U.S. The American Cancer Society estimates 80,550 people will be diagnosed with NHL in 2023. ALL accounts for less than 1% of all cancers in the U.S., with 6,540 new cases estimated in the U.S. in 2023.
Official title:
Phase I/II Study to Evaluate Treatment of Relapsed or Refractory Leukemia and Lymphoma With Universal CRISPR-Cas9 Gene-Editing CAR-T Cells Targeting CD19 and CD20 or CD22
Who:

Contact

Name: Wenying Zhang

Phone: 86-10-55499341

Email: zhangwenying.1984@163.com

Sponsor:

Chinese PLA General Hospital

Partners:
Locations:

China, Beijing

Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital, Beijing, Beijing, China, 100853

Study start:
Jan. 2, 2018
Enrollment:
80 participants
Gene editing method:
CRISPR-Cas9
Type of edit:
Gene knock-out and gene knock-in
Gene:
Anti-CD19/CD20 CAR or anti-CD19/CD22 CAR
Delivery method:
Viral - Ex-vivo
Trial link:
https://clinicaltrials.gov/ct2/show/record/NCT03398967
Other links:

LinkB-cell lymphoma disease informationLinkFrequency of B-cell lymphomaLinkThe Role of Gene Editing Within CAR T-Cell Therapy Development - Interview with Professor Waseem QasimLinkClinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemiaLinkClinical Trial Update – CRISPR-Engineered Dual Specificity CAR-T Therapy

IndicatorIndicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Unknown

Description

CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies. However, a subset of patients relapse due to the loss of CD19 in tumour cells. Dual specificity CD19 and CD20 or CD22 CAR-T cells can recognise and kill the CD19 negative malignant cells through recognition of CD20 or CD22. This is a phase 1/2 study designed to determine the safety of the allogenic gene-edited dual specificity CD19 and CD20 or CD22 CAR-T cells and the feasibility of making enough to treat patients with relapsed or refractory hematological malignancies.

The primary objectives of this trial are :

  • To evaluate the feasibility and safety of universal dual specificity CD19 and CD20 or CD22 CAR-T cells in patients with relapsed or refractory leukaemia and lymphoma.
  • To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry (FCM) analysis of PB, BM and lymph node will be used to detect and quantify survival of universal dual specificity CD19 and CD20 or CD22 CAR-T cells over time.

The secondary objectives of the trial are:

  • For patients with detectable disease, measure anti-tumour response due to universal dual specificity CD19 and CD20 or CD22 CAR-T cell infusions.
  • Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable universal dual specificity CD19 and CD20 or CD22 CAR-T cells (loss of engraftment).

The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using a "split dose" approach to dosing: 10% on day 0, 30% on day 1 and 60% on day 2.

Last updated: Feb. 25, 2024
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