CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.

B-cell Acute Lymphocytic Leukemia Clinical Trial

Official title:

A Study of CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03263208
• Other study ID #: HenanCH152
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: August 24, 2017
• Last updated: October 19, 2017
• Start date: August 16, 2017
• Est. completion date: July 2019

Study information

• Verified date: August 2017
• Source: Henan Cancer Hospital
• Contact: Yongping Song
• Phone: +86 13521186987
• Email: ph200811[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to infusion CD19 CAR-T cells to the patients with relapsed and refractory CD19+ B cell leukemia, to assess the safety and feasibility of this strategy. The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia.

Description:

Upon meeting the eligibility requirements and enrolling on study, Subjects will be collected large numbers of peripheral blood mononuclear cells (PBMC) for the generation of the CD19 CAR-T cells. The T cells are isolated from the PBMC, transduced with a lentivirus to express the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and expanded in vitro and then administered to subjects.

Subjects will have blood tests to assess safety and efficacy, and persistence of the CD19 CAR-T cells on week 4 after their last infusion. Following the 6 months of intensive follow-up, subjects will be evaluated every 10 weeks for 1 year with a physical examination, blood tests, bone marrow aspirate, MRD and persistence of CD19 CAR-T.

Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 70 Years

Eligibility

Inclusion Criteria:

• 1. 2 years to 70 years, expected survival > 3 months;

• 2. CD19 positive B-cell acute lymphoblastic leukemia;

• 3. ECOG < 2;

• 4. The tumor load in the bone marrow is less than 60%;

• 5. Cardiac function: 1-2 levels; Liver: TBIL=3ULN,AST =2.5ULN,ALT =2.5ULN; kidney:

Cr=1.25ULN; Peripheral Blood: WBC = 2.0×109/L, Hb =80 g/L, PLT = 30×109/L);

• 6. No leukemia cells in the central nervous system;

• 7. No serious allergic constitution;

• 8. No other serous diseases that conflicts with the clinical program;

• 9. No other cancer history;

• 10. No serious mental disorder;

• 11. female participants of reproductive potential must have a negative serum pregnancy test;

• 12. Informed consent is signed by a subject or his lineal relation.

Exclusion Criteria:

• 1. Pregnant or lactating women;

• 2. Uncontrolled active infection, HIV infection, syphilis serology reaction positive;

• 3. Active hepatitis B or hepatitis C infection;

• 4. Recent or current use of glucocorticoid or other immunosuppressor;

• 5. With severe cardiac, liver, renal insufficiency, diabetes and other diseases;

• 6. Participate in other clinical research in the past three months; previously treatment with any gene therapy products;

Related Conditions & MeSH terms

• B-cell Acute Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Cyclophosphamide
patients will receive a standard pre-conditioning regime with cyclophosphamide 0.6-0.8g/m2/day IV for 2 days(Day-5 to day-4).
• Fludarabine
Fludarabine 25-30mg/m2/day IV for 3 days(Day-5 to day-3).

Biological:
• CD19 CAR-T
CD19 CAR-T cells will be administered after completion of the chemotherapy.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Henan Cancer Hospital	The Pregene (ShenZhen) Biotechnology Company, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety as assessed by the occurence of study related adverse events	number of participants with adverse events	30 days
Primary	anti-tumor responses of CD19 CAR-T cells		1 year
Secondary	Persistence of the CD19 CAR+ T cells	determine duration of in vivo survival of CD19 CAR-T cells	1 year
Secondary	Number of participants who have T cells ablated with cetuximab	The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery.	1 year