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γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

Primary Purpose

Non-Hodgkin's Lymphoma, Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma, Chronic Lymphoblastic Leukemia

Status

Unknown status

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Autologous γδT cells

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients should sign informed consent form voluntarily.
Gender unlimited, age ≥ 18 years old.
Patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma(PTCL) expect for γδT lymphoma.
Patients had an evaluable imaging lesion of at least greater than 1.5 cm (except CLL).
Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
Adequate bone marrow function as defined by：Absolute neutrophil count (ANC) >1000/mm3；Absolute lymphocyte count (ALC) ≥300/mm3；Platelet ≥50000/mm3；Hemoglobin >8.0g/dl.
Adequate end organ function as defined by: Total bilirubin ≤ 2 x upper limit of normal（ULN）; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 60ml/min.
Male and female of reproductive potential must agree to use birth control during the study and for at least 6 weeks post study.

Exclusion Criteria:

Patients with history of allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
Active central nervous system (CNS) lymphoma; Patients with symptoms of CNS disease must undergo lumbar puncture and brain nuclear magnetic resonance to exclude CNS lymphoma.
Patients receiving chemotherapy within 2 weeks prior to γδT cell infusion, with the following exceptions:
- Pretreatment chemotherapy prescribed by the protocol
- In order to prevent CNS intrathecal chemotherapy (should be stopped 1 week before γδT cell therapy)
- Other exploratory combined medications
Patients with systemic vasculitis, or with active or uncontrolled autoimmune diseases, as well as primary or secondary immunodeficiency diseases.
Active chronic hepatitis B or hepatitis C virus infection, active cytomegalovirus (CMV), EBV infection.
Major surgery that was evaluated by the investigator as unsuitable for inclusion within 4 weeks prior to screening.
History of other malignant tumors, with the following exceptions
- Excisional non-melanoma (e.g. cutaneous basal cell carcinoma)
- Cured situ carcinoma (e.g. cervical carcinoma)
- Localized prostate cancer with radiotherapy or surgery
- Patients with a history of malignant tumors, but the disease has been cured for ≥2 years
Patient's cardiac function meets any of the following conditions
- Left ventricular ejection fraction (LVEF) ≤45%
- Class III or IV heart failure according to the NYHA Heart Failure Classifications
- QTcB>450 msec
- Other cardiac disease that investigators judge is not suitable for enrollment
History of epilepsy or other active central nervous system disorders.
Inoculated live vaccine within 6 weeks before screening.
Uncontrolled serious active infection (such as sepsis, bacteremia and fungemia).
Patients are allergic to cytokines.
Expected survival < 12 weeks.
Participated in any other interventional clinical trial within three months.
Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.

Sites / Locations

Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous γδT cells

Arm Description

Subjects will receive 3 cycles of γδT cells treatments, at four-week intervals, each cycle has 2 infusions, single infusion intravenously at a target dose of 1~2×10e9 γδT cells (constant dose).

Outcomes

Primary Outcome Measures

Number of Participants with Severe/Adverse Events as a Measure of Safety.

Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.

Overall response rate (ORR)

Rate of complete remission (CR) and partial remission (PR).

Secondary Outcome Measures

Duration of remission (DOR)

Duration of remission is defined as the time from the first occurrence of CR or PR in the tumor assessment to the first occurrence of disease progression (PD) or death.

Time to response(TTR)

Time to response is defined as the time from the first administration of trial drug to the first occurrence of CR or PR in the tumor assessment.

Disease control rate (DCR)

Disease control rate is defined as the proportion of subjects who achieved CR, PR, and disease stability (SD) by imaging evaluation.

Progression free survival (PFS)

Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.

Overall survival (OS)

Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.

Full Information

NCT ID

NCT04028440

First Posted

July 18, 2019

Last Updated

September 24, 2019

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Collaborators

Beijing GD Initiative Cell Therapy Technology Co., Ltd., Chinese Academy of Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT04028440

Brief Title

γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

Official Title

Preliminary Exploration of γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL).

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Unknown status

Study Start Date

October 2019 (Anticipated)

Primary Completion Date

December 31, 2020 (Anticipated)

Study Completion Date

March 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Collaborators

Beijing GD Initiative Cell Therapy Technology Co., Ltd., Chinese Academy of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study aims to evaluate the safety and efficacy of autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.

Detailed Description

This is a single-centre, non-randomised, open label, no control, prospective clinical trial. The study will include the following sequential phases: sign informed consent, γδT cells pre-culture, screening and registration to the trial, apheresis, γδT cells preparation, pre-treatment for lymphodepleting chemotherapy (selectable plan), treatment and follow-up. The study will evaluate the safety and efficacy of the autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.

6. Conditions and Keywords

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

Non-Hodgkin's Lymphoma, Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma, Chronic Lymphoblastic Leukemia, Peripheral T Cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Biological: Autologous γδT cells Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Autologous γδT cells

Arm Type

Experimental

Arm Description

Subjects will receive 3 cycles of γδT cells treatments, at four-week intervals, each cycle has 2 infusions, single infusion intravenously at a target dose of 1~2×10e9 γδT cells (constant dose).

Intervention Type

Biological

Intervention Name(s)

Autologous γδT cells

Intervention Description

Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.

Primary Outcome Measure Information:

Title

Number of Participants with Severe/Adverse Events as a Measure of Safety.

Description

Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.

Time Frame

15 months

Title

Overall response rate (ORR)

Description

Rate of complete remission (CR) and partial remission (PR).

Time Frame

28 days after infusion of γδT cells

Secondary Outcome Measure Information:

Title

Duration of remission (DOR)

Description

Duration of remission is defined as the time from the first occurrence of CR or PR in the tumor assessment to the first occurrence of disease progression (PD) or death.

Time Frame

15 months

Title

Time to response(TTR)

Description

Time to response is defined as the time from the first administration of trial drug to the first occurrence of CR or PR in the tumor assessment.

Time Frame

15 months

Title

Disease control rate (DCR)

Description

Disease control rate is defined as the proportion of subjects who achieved CR, PR, and disease stability (SD) by imaging evaluation.

Time Frame

15 months

Title

Progression free survival (PFS)

Description

Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.

Time Frame

15 months

Title

Overall survival (OS)

Description

Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.

Time Frame

15 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients should sign informed consent form voluntarily. Gender unlimited, age ≥ 18 years old. Patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma(PTCL) expect for γδT lymphoma. Patients had an evaluable imaging lesion of at least greater than 1.5 cm (except CLL). Eastern Cooperative Oncology Group (ECOG) Performance status 0-2. Adequate bone marrow function as defined by：Absolute neutrophil count (ANC) >1000/mm3；Absolute lymphocyte count (ALC) ≥300/mm3；Platelet ≥50000/mm3；Hemoglobin >8.0g/dl. Adequate end organ function as defined by: Total bilirubin ≤ 2 x upper limit of normal（ULN）; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 60ml/min. Male and female of reproductive potential must agree to use birth control during the study and for at least 6 weeks post study. Exclusion Criteria: Patients with history of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Active central nervous system (CNS) lymphoma; Patients with symptoms of CNS disease must undergo lumbar puncture and brain nuclear magnetic resonance to exclude CNS lymphoma. Patients receiving chemotherapy within 2 weeks prior to γδT cell infusion, with the following exceptions: Pretreatment chemotherapy prescribed by the protocol In order to prevent CNS intrathecal chemotherapy (should be stopped 1 week before γδT cell therapy) Other exploratory combined medications Patients with systemic vasculitis, or with active or uncontrolled autoimmune diseases, as well as primary or secondary immunodeficiency diseases. Active chronic hepatitis B or hepatitis C virus infection, active cytomegalovirus (CMV), EBV infection. Major surgery that was evaluated by the investigator as unsuitable for inclusion within 4 weeks prior to screening. History of other malignant tumors, with the following exceptions Excisional non-melanoma (e.g. cutaneous basal cell carcinoma) Cured situ carcinoma (e.g. cervical carcinoma) Localized prostate cancer with radiotherapy or surgery Patients with a history of malignant tumors, but the disease has been cured for ≥2 years Patient's cardiac function meets any of the following conditions Left ventricular ejection fraction (LVEF) ≤45% Class III or IV heart failure according to the NYHA Heart Failure Classifications QTcB>450 msec Other cardiac disease that investigators judge is not suitable for enrollment History of epilepsy or other active central nervous system disorders. Inoculated live vaccine within 6 weeks before screening. Uncontrolled serious active infection (such as sepsis, bacteremia and fungemia). Patients are allergic to cytokines. Expected survival < 12 weeks. Participated in any other interventional clinical trial within three months. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.

Central Contact Person:

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

Dehui Zou, Dr.

Phone

86-022-23909283

zoudehui@ihcams.ac.cn

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

Shuhua Yi, Dr.

Phone

86-022-23909106

yishuhua@ihcams.ac.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dehui Zou, Dr.

Organizational Affiliation

Institute of Hematology & Blood Disease Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Hematology & Blood Diseases Hospital

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dehui Zou, Dr.

Phone

86-022-23909283

zoudehui@ihcams.ac.cn

First Name & Middle Initial & Last Name & Degree

Shuhua Yi, Dr.

Phone

86-022-23909106

yishuhua@ihcams.ac.cn

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

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