Anti-CD19 CAR-T Therapy Bridging to HSCT for CD19+ B-Cell Malignancies

A Phase 1/2 Study Evaluating the Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-Modified T Cell (CAR-T) Therapy Bridging to Hematological Stem Cell Transplantation (HSCT) for Relapsed/Refractory CD19+ B-Cell Malignancies

This is the second stage of the previous anti-CD19 CAR-T therapy (NCT02965092). The study aims to evaluate the safety and efficacy of consolidative allo-HSCT following CAR-T therapy in patients with relapsed or refractory B cell Malignancies.

Study Overview

• Status: Unknown
• Conditions: B Cell Lymphoma; Acute Lymphoblastic Leukemia
• Intervention / Treatment: Procedure: Allogeneic hematological stem cell transplantation

Detailed Description

Anti-CD19 CAR-T therapy has been confirmed effective for relapsed/refractory B-cell malignancies. However, its ability to keep patients in maintained remission is limited. In order to keep patients in long-term remissions, patients who had achieved MRD-negative complete remissions through CAR-T therapy (NCT02965092) will, on their own accord, receive allo-HSCT if there are no previous HSCT, contraindications, and other restrictions.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: HENG MEI, M.D., Ph.D; Phone Number: 86-13886160811; Email: mayheng@126.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: HENG MEI, M.D., Ph.D; Phone Number: 86-13886160811; Email: mayheng@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient is pathologically and histologically confirmed as CD19 + B cell malignancies, and has achieved MRD-negative CR through CAR-T therapy (NCT02965092);

2. B cell hematological malignancies include the following three categories:

   • B-cell acute lymphocytic leukemia (B-ALL);
   • Indolent B-cell lymphoma (CLL, FL, MZL, LPL);
   • Aggressive B-cell lymphoma (DLBCL, BL, MCL);
3. < 70 years old;
4. Expected survival time > 6 months;
5. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
6. Voluntarily participate in this experiment and sign informed consent by themselves, or legally authorized representative.

Exclusion Criteria:

1. With a history of epilepsy or other central nervous system diseases;
2. Previous allogeneic hematopoietic stem cell transplantation;
3. The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);
4. Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
5. Not curable active infection;
6. Patients with active hepatitis B or hepatitis C virus infection;
7. Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
8. Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);
9. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
10. Patients with HIV-infection;
11. Any situation that may increase the risk of patients or interfere with test results.

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: Consolidative allo-HSCT following CAR-T therapy; Patients who had achieved MRD-negative complete remissions through CAR-T therapy (NCT02965092) will, on their own accord, receive allo-HSCT if there are no previous HSCT, contraindications, and other restrictions.	Procedure: Allogeneic hematological stem cell transplantation; Patients receive allogeneic hematological stem cell transplantation after they achieve MRD- CR through CAR-T therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	To evaluate the safety of anti-CD19 CAR-T therapy bridging to allo-HSCT. Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS was calculated from the date of inclusion to death or last follow-up (censored).	5 years
Event-free survival	EFS was calculated from the date of inclusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).	5 years
Relapse-free survival	RFS was calculated from the date of inclusion to relapse or last visit (censored).	5 years

Collaborators and Investigators

• Sponsor: Wuhan Sian Medical Technology Co., Ltd
• Collaborators: Wuhan Union Hospital, China; Xiangyang Central Hospital; Jingzhou Central Hospital; People Hospital Of Yichang
• Investigators: Principal Investigator: YU HU, M.D., Ph.D, Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2016
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 8, 2019
• Last Verified: May 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, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: CART-CD19-02

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