A Feasibility and Safety Study of CD38 CAR-T Cell Immunotherapy for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy

Phase I/II Study to Evaluate Treatment of Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy With CAR-T Cells Targeting CD38

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 tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD38. This is a phase 1/2 study designed to determine the safety of the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy.

Study Overview

• Status: Unknown
• Conditions: Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T ACI
• Intervention / Treatment: Biological: Specificity CD38 CAR-T Cells

Detailed Description

1. PRIMARY OBJECTIVES:

   1. To evaluate the feasibility and safety of specificity CD38 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma.
   2. 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 CD38 CAR-T cells over time.

2. SECONDARY OBJECTIVES:

   1. For patients with detectable disease, measure anti-tumor response due to specificity CD38 CAR-T cell infusions.
   2. The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0: 1-5x10e6/kg total dose on day 0.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hejin Jia; Phone Number: 86-10-55499341; Email: PLAGH@QQ.COM
• Study Contact Backup: Name: Zhitao Gao, Dr; Phone Number: 86-010-66937917; Email: zhitaogao@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100083
      • Recruiting
      • Biotherapeutic Department and Hematology Department of Chinese PLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female participant
2. 12 Years to 70 Years (Child, Adult, Senior)
3. Patient with relapsed CD38+ B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy
4. Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
6. Adequate organ function

Exclusion Criteria:

1. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
2. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
3. Richter's syndrome
4. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
5. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
6. Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
7. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
8. Patient has an investigational medicinal product within the last 30 days prior to screening
9. Previous treatment with investigational gene or cell therapy medicine products
10. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
11. Pregnant or nursing women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability		24 weeks
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes		24 weeks
MTD of specificity CD38 CAR-T cells	The highest dose of specificity CD38 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of specificity CD38 CAR-T cells.	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Six-month Objective response rate of complete remission and partial remission	24 weeks
Six-month Overall survival	24 weeks
Six-month Progression free survival	24 weeks

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 23, 2018
• Primary Completion (ANTICIPATED): November 23, 2022
• Study Completion (ANTICIPATED): November 23, 2022

Study Registration Dates

• First Submitted: November 24, 2018
• First Submitted That Met QC Criteria: November 24, 2018
• First Posted (ACTUAL): November 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 7, 2018
• Last Update Submitted That Met QC Criteria: December 5, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: CHN-PLAGH-BT-038

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