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

Primary Purpose

Acute Lymphoblastic Leukemia, B Cell Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Second generation CAR-T cells

Hematological stem cell transplantation

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

undefined - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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;
The patient is MRD+ (<10%) after at least two cycles of chemotherapies.
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);
< 70 years old;
Expected survival time > 6 months;
Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
Voluntarily participate in this experiment and sign informed consent by themselves, or legally authorized representative.

Exclusion Criteria:

With a history of allo-HSCT;
With a history of epilepsy or other central nervous system diseases;
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);
Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
Not curable active infection;
Patients with active hepatitis B or hepatitis C virus infection;
Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
Using product of gene therapy before;
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);
Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
Patients with HIV-infection;
Any situation that may increase the risk of patients or interfere with test results.

Sites / Locations

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination of CAR-T therapy and HSCT

Arm Description

After patients achieve MRD- remissions through Second generation CAR-T cells, they will subsequently receive hematological stem cell transplantations within 30 days.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT03366324

First Posted

December 1, 2017

Last Updated

November 18, 2018

Sponsor

Wuhan Sian Medical Technology Co., Ltd

Collaborators

Wuhan Union Hospital, China, Jingzhou Central Hospital, Xiangyang Central Hospital, The First People's Hospital of Yuhang District

1. Study Identification

Unique Protocol Identification Number

NCT03366324

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Unknown status

Study Start Date

May 1, 2016 (Actual)

Primary Completion Date

January 1, 2021 (Anticipated)

Study Completion Date

June 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wuhan Sian Medical Technology Co., Ltd

Collaborators

Wuhan Union Hospital, China, Jingzhou Central Hospital, Xiangyang Central Hospital, The First People's Hospital of Yuhang District

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia, B Cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

The only one group of patients will receive the combination of CAR-T therapy and HSCT.

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Combination of CAR-T therapy and HSCT

Arm Type

Experimental

Arm Description

After patients achieve MRD- remissions through Second generation CAR-T cells, they will subsequently receive hematological stem cell transplantations within 30 days.

Intervention Type

Genetic

Intervention Name(s)

Second generation CAR-T cells

Intervention Description

Patients receive CD19 CAR-T cells transduced with a lentiviral vector on days 0, 1, and 2.

Intervention Type

Procedure

Intervention Name(s)

Hematological stem cell transplantation

Intervention Description

Patients receive hematological stem cell transplantations within 3 months after they achieve MRD- remissions after CAR-T therapies.

Primary Outcome Measure Information:

Title

Occurrence of study related adverse events

Description

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

Time Frame

200 days from enrollment

Secondary Outcome Measure Information:

Title

Number of participants with an MRD negative complete remission after CAR-T therapy and HSCT

Description

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

Time Frame

2 years from enrollment

10. Eligibility

Sex

All

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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; The patient is MRD+ (<10%) after at least two cycles of chemotherapies. 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); < 70 years old; Expected survival time > 6 months; Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit; Voluntarily participate in this experiment and sign informed consent by themselves, or legally authorized representative. Exclusion Criteria: With a history of allo-HSCT; With a history of epilepsy or other central nervous system diseases; 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); Pregnant or lactating women (safety of this therapy for the unborn child is unknown); Not curable active infection; Patients with active hepatitis B or hepatitis C virus infection; Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently); Using product of gene therapy before; 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); Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial; Patients with HIV-infection; Any situation that may increase the risk of patients or interfere with test results.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

YU HU, M.D., Ph.D

Phone

86-13986183871

dr_huyu@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

HENG MEI, M.D., Ph.D

Phone

86-13886160811

mayheng@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

YU HU, M.D., Ph.D

Organizational Affiliation

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

City

Wuhan

State/Province

Hubei

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

YU HU, M.D., Ph.D

Phone

86-13986183871

dr_huyu@126.com

First Name & Middle Initial & Last Name & Degree

HENG MEI, M.D., Ph.D

Phone

86-13886160811

mayheng@126.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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