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

B-cell Acute Lymphoblastic Leukemia (B-ALL) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04166838
• Other study ID #: V1.0
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 8, 2019
• Est. completion date: November 8, 2019

Study information

• Verified date: November 2019
• Source: Shanghai Longyao Biotechnology Inc., Ltd.
• Contact: Tengfeng Ni, Master
• Phone: +86 021- 66289710
• Email: nitengfeng[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 8, 2019
• Est. primary completion date: November 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia (B-ALL)
• Burkitt Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Safety and Efficacy of CD19 UCAR-T Cells

Intervention

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.

Locations

Country	Name	City	State
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Longyao Biotechnology Inc., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Adverse events (AEs)	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	24 weeks
Primary	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
Primary	Expression of CD19 UCART cells	Expression of CD19 UCART cells detected by flow cytometry in blood and bone marrow.	2 years
Primary	Detection of CD19 UCART cells	Detection of CD19 UCART cells in blood, bone marrow by Quantitative Polymerase Chain Reaction (q-PCR).	2 years
Secondary	Overall Remission Rate (ORR)		2 years
Secondary	Complete Remission (CR)		2 years
Secondary	Disease Stabilization (SD)		2 years
Secondary	Disease Progression (PD)		2 years
Secondary	Overall survival (OS)		2 years
Secondary	Progression-free survival (PFS)		2 years
Secondary	Disease-free survival (DFS)		2 years