The Clinical Study of CD19 UCAR-T Cells in Patients With B-cell Acute Lymphoblastic Leukemia (B-ALL)

This is a single arm, open-label, single center, exploratory clinical study to evaluate the safety and efficacy of CD19 UCAR-T Cells in Patients With CD19+ B-cell acute lymphoblastic leukemia (B-ALL).

Study Overview

• Status: Unknown
• Conditions: B-cell Acute Lymphoblastic Leukemia (B-ALL); Safety and Efficacy of CD19 UCAR-T Cells
• Intervention / Treatment: Biological: CD19 UCARTcells

Detailed Description

This study did not set up a control group. The maximum dose was determined according to the dose escalation test. Based on the number of CART cells per kg body weight which was proved to be safe and effective, all the subjects were treated with one single dose of CD19 UCART cells per treatment course. The dose escalation test was designed to evaluate the three dose levels of CD19 UCART (1 × 10 ^ 6 cells/kg,3 × 10 ^ 6 cells/kg,5 × 10 ^ 6 cells/kg). Each CD19 UCART infusion will be carried out on day 0. Each subject was observed for at least 4 weeks after the last infusion. If there was no dose-limited toxicity (DLT), it is necessary to continue multiple treatment courses at this dose level. The detailed administration time and dose were decided by the researchers.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Principal Investigator: Jiang Cao
      • Contact: Jiang Cao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Subjects between 6 and 70 years of age, inclusive.

• 2. Subjects diagnosed as relapsed or refractory B cell acute lymphocytic leukemia (B-ALL):

  1. Relapse as defined by 2nd or greater BM relapse or Any BM relapse after allogeneic SCT, naive lymphocytes in BM≥5%；
  2. refractory as defined by not achieving a CR after 2 rounds of standard chemotherapy.
• 3. Life expectancy > 12 weeks.
• 4. ECOG score between 0 and 1.

• 5. Liver, Renal, Heart and Lungs function defined as:

  1. Creatininec≤1.5 ULN;
  2. ALT/AST ≤2.5 ULN;
  3. Total Bilirubin≤1.5×ULN;
  4. Pulse oxygenation≥92%;
  5. Left Ventricular Shortening Fraction (LVSF)≥50%;
• 6. Subjects could comprehend the clinical study and able to provide written consent at the time of consent or assent.

Exclusion Criteria:

• 1. Pregnant or lactating women, or men or women with pregnancy plans within 6 months.
• 2. Subjects with contagious disease，such as HIV, active HBV and HCV, and syphilis, etc.
• 3. Subjects with mental or psychological illness who cannot be combined with treatment and efficacy evaluation.
• 4. Subjects with severe autoimmune disease and long-term use of immunosuppressants.
• 5. Subjects with active or uncontrollable infections requiring systemic treatment within 14 days prior to enrollment.
• 6. Subjects with any unstable systemic disease including, but not limited to, active infection (except for local infection), unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ III).
• 7. subjects combined with dysfunction of vital organs such as lung, brain and kidney.
• 8. subjects that Participated in other similar clinical trials within 6 months.
• 9. subjects currently receiving treatment for other gene therapy.
• 10. subjects combined with graft versus host disease (GVHD).
• 11. Other subjects judged by the researchers to be unsuitable for admission to the study.

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: CD19 UCAR-T

Biological: CD19 UCARTcells; This study did not set up a control group. The maximum dose was determined according to the dose escalation test. Based on the number of CART cells per kg body weight which was proved to be safe and effective, all the subjects were treated with one single dose of CD19 UCART cells per treatment course. The dose escalation test was designed to evaluate the three dose levels of CD19 UCART (1 × 10 ^ 6 cells/kg,3 × 10 ^ 6 cells/kg,5 × 10 ^ 6 cells/kg). Each CD19 UCART infusion will be carried out on day 0. Each subject was observed for at least 4 weeks after the last infusion. If there was no dose-limited toxicity (DLT), it is necessary to continue multiple treatment courses at this dose level. The detailed administration time and dose were decided by the researchers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Adverse events (AEs)	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	24 weeks
Graft-versus-Host Disease (GVHD)	Number of Participants with the GVHD by monitoring the epithelial cell damage in target organs including skin, liver, and gastrointestinal tract.	42 days
Expression of CD19 UCART cells	Expression of CD19 UCART cells detected by flow cytometry in blood and bone marrow.	2 years
Detection of CD19 UCART cells	Detection of CD19 UCART cells in blood, bone marrow by Quantitative Polymerase Chain Reaction (q-PCR).	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	2 years
Progression-free survival (PFS)	2 years
Complete Remission (CR)	2 years
Overall Remission Rate (ORR)	2 years
Disease Stabilization (SD)	2 years
Disease Progression (PD)	2 years
Disease-free survival (DFS)	2 years

Collaborators and Investigators

• Sponsor: Shanghai Longyao Biotechnology Inc., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 8, 2019
• Primary Completion (Anticipated): November 8, 2019
• Study Completion (Anticipated): November 8, 2019

Study Registration Dates

• First Submitted: November 10, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: November 1, 2019

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: V1.0

Drug and device information, study documents

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