Back to resultsAllogeneic γ9δ2 T Cells Treatment of Recurrent Hematologic Tumors
Primary Purpose
Hematologic Diseases
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
allogeneic γ9δ2 T Cells
Fludarabine
Cyclophosphamide
Zoredronic acid
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Diseases focused on measuring Recurrent hematologic tumors, Allogenic γδT Cell
Eligibility Criteria
Inclusion Criteria: Age 12-65 (inclusive)； Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation； Basically normal liver and kidney function (as demonstrated by the following laboratory tests prior to initial γ9δ2 T cell therapy) Alanine transaminase/aspartate transaminase < 2.5×ULN； serum creatinine < 1.5×ULN； total bilirubin level < 1.5×ULN； No obvious hereditary disease; Normal cardiac function, cardiac ejection index above 55%; Women of reproductive age (15 to 49 years) must undergo a pregnancy test within 7 days before starting treatment and the result is negative, and use contraception during the clinical trial period and within 3 months after the last cell transfusion; Sign informed consent. Exclusion Criteria: Patients with simple extramedullary recurrence; Pregnant and lactating women; Organ failure; Heart: Ⅲ level and Ⅳ level; Liver: reach the grade C Child - Turcotte liver function; Kidney, renal failure and uremia period; Lung: symptoms of severe respiratory failure; Brain: consciousness disorder. Patients with a history of solid organ transplantation; Uncontrollable infectious diseases or other serious diseases, including but not limited to infections (such as HIV positive), congestive heart failure, unstable angina, arrhythmia, psychosis, or restricted social circumstances or those that the attending physician considers to pose unpredictable risks; Patients with systemic autoimmune diseases or primary immunodeficiency; Patients with allergic constitution; Use of systemic steroid drugs; Chronic diseases requiring the use of immunological agents or hormone herapy; Prior treatment with any other immune cells; Participated in similar clinical trials within 30 days; Received radiation therapy within 4 weeks from the time of enrollment; Researchers don't think clinical trials are appropriate for other reasons.
Sites / Locations
- Anhui Provincial HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation
Arm Description
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells
Outcomes
Primary Outcome Measures
Incidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic γ9δ2 T cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0
Incidence of Dose-Limiting Toxicities (DLTs)
DLT was defined as allogeneic γ9δ2 T Cells-related events with onset within first 14 days following infusion:
The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting > 2 weeks; Any allogeneic γ9δ2 T cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Maximum tolerated dose (MTD)
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
Recommended phase 2 dose (RP2D)
The recommended dose for phase 2 was determined through phase 1 study
Secondary Outcome Measures
Overall Survival (OS)
OS is defined as the time from allogeneic γ9δ2 T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Progression Free Survival (PFS)
PFS is defined as the time from the allogeneic γ9δ2 T cells infusion date to the date of disease progression assessed by investigators assessment, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Pharmacokinetics: Persistence of the allogeneic γ9δ2 T cells
Persistence of the allogeneic γ9δ2 T cells assessed by number in peripheral blood.
Pharmacodynamics: Peak level of cytokines in serum
The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α) etc. Peak was defined as the maximum post-baseline level of the cytokine.
Full Information
NCT ID
NCT05755854
First Posted
February 23, 2023
Last Updated
September 21, 2023
Sponsor
Anhui Provincial Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05755854
Brief Title
Allogeneic γ9δ2 T Cells Treatment of Recurrent Hematologic Tumors
Official Title
Allogeneic γ9δ2 T Cells for the Treatment of Recurrent Hematologic Tumors After Allogeneic Hematopoietic Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 3, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Anhui Provincial Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open single-arm clinical study aimed at evaluating the safety and tolerance of allogeneic γ9δ2 T cell injection in the treatment of patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation.
Detailed Description
To evaluate the safety and in vivo dynamics of allogeneic γ9δ2 T cell in the treatment of recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation patients, and to explore the appropriate therapeutic dose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Diseases
Keywords
Recurrent hematologic tumors, Allogenic γδT Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation
Arm Type
Experimental
Arm Description
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells
Intervention Type
Biological
Intervention Name(s)
allogeneic γ9δ2 T Cells
Intervention Description
dose escalation (3+3) : dose 1 (5 × 10^7cells/kg) ,dose 2 (1 × 10^8 cells/kg) ,dose 3 (2 × 10^8cells/kg)
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabine Phosphate for Injection
Intervention Description
Intravenous fludarabine on days-5 and -4,the infusion dose is adjusted according to the subject's condition
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cyclophosphamide for Injection
Intervention Description
Intravenous cyclophosphamide on days -5、-4、and -3, the infusion dose is adjusted according to the subject's condition
Intervention Type
Drug
Intervention Name(s)
Zoredronic acid
Intervention Description
Intravenous zoredronic acid 50ug/kg 24 hours before cell infusion（or according to the dosage of the instruction）（If applicable）
Primary Outcome Measure Information:
Title
Incidence of Adverse Events (AEs)
Description
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic γ9δ2 T cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0
Time Frame
12 months
Title
Incidence of Dose-Limiting Toxicities (DLTs)
Description
DLT was defined as allogeneic γ9δ2 T Cells-related events with onset within first 14 days following infusion:
The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting > 2 weeks; Any allogeneic γ9δ2 T cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Time Frame
First infusion date of allogeneic γ9δ2 T cells to 14 days end cell infusion
Title
Maximum tolerated dose (MTD)
Description
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
Time Frame
14 days
Title
Recommended phase 2 dose (RP2D)
Description
The recommended dose for phase 2 was determined through phase 1 study
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS is defined as the time from allogeneic γ9δ2 T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Time Frame
12 months
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the allogeneic γ9δ2 T cells infusion date to the date of disease progression assessed by investigators assessment, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Time Frame
12 months
Title
Pharmacokinetics: Persistence of the allogeneic γ9δ2 T cells
Description
Persistence of the allogeneic γ9δ2 T cells assessed by number in peripheral blood.
Time Frame
14 days
Title
Pharmacodynamics: Peak level of cytokines in serum
Description
The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α) etc. Peak was defined as the maximum post-baseline level of the cytokine.
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 12-65 (inclusive)；
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation；
Basically normal liver and kidney function (as demonstrated by the following laboratory tests prior to initial γ9δ2 T cell therapy)
Alanine transaminase/aspartate transaminase < 2.5×ULN；
serum creatinine < 1.5×ULN；
total bilirubin level < 1.5×ULN；
No obvious hereditary disease;
Normal cardiac function, cardiac ejection index above 55%;
Women of reproductive age (15 to 49 years) must undergo a pregnancy test within 7 days before starting treatment and the result is negative, and use contraception during the clinical trial period and within 3 months after the last cell transfusion;
Sign informed consent.
Exclusion Criteria:
Patients with simple extramedullary recurrence;
Pregnant and lactating women;
Organ failure;
Heart: Ⅲ level and Ⅳ level;
Liver: reach the grade C Child - Turcotte liver function;
Kidney, renal failure and uremia period;
Lung: symptoms of severe respiratory failure;
Brain: consciousness disorder.
Patients with a history of solid organ transplantation;
Uncontrollable infectious diseases or other serious diseases, including but not limited to infections (such as HIV positive), congestive heart failure, unstable angina, arrhythmia, psychosis, or restricted social circumstances or those that the attending physician considers to pose unpredictable risks;
Patients with systemic autoimmune diseases or primary immunodeficiency;
Patients with allergic constitution;
Use of systemic steroid drugs;
Chronic diseases requiring the use of immunological agents or hormone herapy;
Prior treatment with any other immune cells;
Participated in similar clinical trials within 30 days;
Received radiation therapy within 4 weeks from the time of enrollment;
Researchers don't think clinical trials are appropriate for other reasons.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhu Xiaoyu, Ph.D
Phone
+86 15255456091
Email
xiaoyuz@ustc.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Sun Guangyu
Phone
+86 13956970687
Email
sunguangyu_vip@foxmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhu Xiaoyu, Ph.D
Organizational Affiliation
Director of Hematology Department, Anhui Provincial Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anhui Provincial Hospital
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230036
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhu Xiaoyu, Ph.D
Phone
+86 15255456091
Email
xiaoyuz@ustc.edu.cn
First Name & Middle Initial & Last Name & Degree
Sun Guangyu
Phone
+86 13956970687
Email
sunguangyu_vip@foxmail.com
12. IPD Sharing Statement
Learn more about this trial
Allogeneic γ9δ2 T Cells Treatment of Recurrent Hematologic Tumors
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