Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL

• Sponsor: Zhujiang Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03407859
• Collaborator: Nanfang Hospital of Southern Medical University (Other)
• Enrollment: 30
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 74.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients. CD20/CD22/CD10 is still expressed in CD19 negative B-ALL cells which means these CD molecules may become new targets in treatment of CD19-negative relapse of B-ALL. Thus sequential treatment with CD20/CD22/CD10-CART after CD19-CART treatment in relapsed/refractory B-ALL will kill and eliminate CD19 negative B-ALL cells and prolong the remission time.

Condition or Disease	Intervention/Treatment	Phase
Therapy Related Leukemia	Biological: Sequential Treatment With different CART	Early Phase 1

Detailed Description

B-cell acute lymphoblastic leukemia is the most common type of leukemia and the prognosis of relapsed/refractory B-ALL is poor. Chimeric Antigen Receptor-transduced T cell (CAR-T) therapy is one of revolutionary targeted immunotherapy. CD19 CAR-T is the most commonly used engineered T cell in B-ALL. The treatment effect is significant and far more than traditional therapy in relapsed/refractory B-ALL. However, the remission time after CD19 CAR-T infusion is short.CD19-positive and CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients The cause of relapse after CAR-T infusion is minimal residual disease (MRD) which will induce CD19 negative relapse. CD20/CD22/CD10 is still expressed in CD19 negative B-ALL cells which means these CD molecules may become new targets in treatment of CD19 negative relapse of B-ALL. Thus sequential treatment with CD20/CD22/CD10-CART after CD19-CART treatment in relapsed/refractory B-ALL will kill and eliminate CD19 negative B-ALL cells and prolong the remission time.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL
• Actual Study Start Date: Jan 18, 2016
• Anticipated Primary Completion Date: Dec 31, 2021
• Anticipated Study Completion Date: Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequential therapy with different CART Sequential therapy With different CART including one kind of CD20/CD22/CD10-CART After CD19-CART therapy in CD19-negative relapse ALL patients, subjects will receive 1-5 x 10^6/Kg transduced CAR T cells at one time.	Biological: Sequential Treatment With different CART; Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment in Relapsed/Refractory B-ALL

Outcome Measures

Primary Outcome Measures

1. Adverse events that Are related to treatment [2 years]

   Determine the toxicity profile of the CD19-targeted and CD20/CD22/CD10-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

1. Estimate 2 year overall survival(OS) after infusion of CD19-CART and sequential treatment [2 years]

   To estimate 2 year overall survival(OS) after CD19-CART infusion and sequential treatment with Relapsed/Refractory B-ALL

2. Estimate relapse rate after infusion of CD19-CART and sequential treatment [4 years]

   To estimate relapse rate after CD19-CART infusion and sequential treatment with Relapsed/Refractory B-ALL

3. Estimate 2 year progression free survival after infusion of CD19-CART and sequential treatment [2 years]

   To estimate 2 year progression free survival (PFS) after CD19-CART infusion and sequential treatment with Relapsed/Refractory B-ALL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Relapsed/Refractory B-ALL patients

2. Did not achieve complete remission after 2 times of standard plan chemotherapy

3. Relapsed after first induction chemotherapy

4. Did not response to chemotherapy before HSCT or relapsed after HSCT

5. Cannot receive allo-HSCT or refuse to receive allo-HSCT

6. Relapsed after CD19-CART infusion

7. MRD monitoring confirmed positive(MRD>0.01%) after CD19-CART infusion

8. Cell phenotype is CD19 negative and CD20/CD22/CD10 positive (single or combined) after CD19-CART therapy

9. Estimated survival time is more than 3 months in leukemia

10. Volunteered for this clinical trail and signed a consent form

Exclusion Criteria:

1. MRD was negative after CD19-CART therapy

2. MRD was negative while the cell phenotype was CD19 expressed

3. Patients with severe insufficient cardiac, pulmonary and hepatorenal functions

4. Patients with severe mental illness, neurological disease or infectious disease

5. Patients with GVHD was taking immunosuppressants

6. Pregnant or lactating women

7. Patients have received other genetic therapy products

8. Transfection efficiency was less than 30%

9. Any situation may do harm to the subjects or interfere the results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Medical University Zhujiang Hospital	Guangdong	Guangdong	China	510000

Sponsors and Collaborators

• Zhujiang Hospital
• Nanfang Hospital of Southern Medical University

Investigators

• Principal Investigator: Yanjie He, Ph.D, Zhujiang Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zhujiang Hospital
• ClinicalTrials.gov Identifier: NCT03407859
• Other Study ID Numbers: 2016-XYNK-002
• First Posted: Jan 23, 2018
• Last Update Posted: Aug 10, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Zhujiang Hospital: CD19-CART; CD20-CART; CD10-CART; CD22-CART; Relapsed/Refractory B-ALL; MRD

Study Results

No Results Posted as of Aug 10, 2021