Anti-CD19 CAR-T Therapy Combine With HSCT to Treat MRD+ B-cell Malignancies

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

For micro residual disease (MRD) positive patients who have undergone at least 2 cycles chemotherapies for their CD19+ B-cell malignancies, there would be much more risks for them to receive hematological stem cell transplantation (HSCT) than MRD- patients. In order to reduce HSCT-related adverse events for these kind of patients, investigators plan to conduct CAR-T therapies on them first to make them achieve MRD- statuses, and then transfer them to HSCT.

Study Overview

• Status: Unknown
• Conditions: B Cell Lymphoma; Acute Lymphoblastic Leukemia
• Intervention / Treatment: Genetic: Second generation CAR-T cells; Procedure: Hematological stem cell transplantation

Detailed Description

In order to improve prognoses for MRD+ patients who have undergone at least 2 cycles chemotherapies, patients will receive CAR-T therapy before HSCT, once they achieve MRD- remissions, they will subsequently receive HSCT if there are no contraindications.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• 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
      • Institute of Hematology, 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 tumors, and has no effective treatment options currently, such as chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT); or patients voluntarily choose CD19 CAR-T cells as a first treatment;
2. The patient is MRD+ (<10%) after at least two cycles of chemotherapies.

3. 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);
4. < 70 years old;
5. Expected survival time > 6 months;
6. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
7. Voluntarily participate in this experiment and sign informed consent by themselves, or legally authorized representative.

Exclusion Criteria:

1. With a history of allo-HSCT;
2. With a history of epilepsy or other central nervous system diseases;
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. Using product of gene therapy before;
9. 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);
10. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
11. Patients with HIV-infection;
12. 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: Combination of CAR-T therapy and HSCT; After patients achieve MRD- remissions through Second generation CAR-T cells, they will subsequently receive hematological stem cell transplantations within 30 days.	Genetic: Second generation CAR-T cells; Patients receive CD19 CAR-T cells transduced with a lentiviral vector on days 0, 1, and 2.; Procedure: Hematological stem cell transplantation; Patients receive hematological stem cell transplantations within 3 months after they achieve MRD- remissions after CAR-T therapies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of study related adverse events	defined as >= Grade 3（NCI CTCAE version 4.03） signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment	200 days from enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with an MRD negative complete remission after CAR-T therapy and HSCT	the efficacy of the combination of CAR-T therapy and HSCT will be estimated based on the number of participants who have an MRD negative (flow cytometry) bone marrow aspirate following the treatment	2 years from enrollment

Collaborators and Investigators

• Sponsor: Wuhan Sian Medical Technology Co., Ltd
• Collaborators: Wuhan Union Hospital, China; Xiangyang Central Hospital; Jingzhou Central Hospital; The First People's Hospital of Yuhang District
• Investigators: Principal Investigator: YU HU, M.D., Ph.D, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 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): November 20, 2018
• Last Update Submitted That Met QC Criteria: November 18, 2018
• Last Verified: November 1, 2018

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-CD19-03

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