Allogeneic γ9δ2 T Cells Treatment of Recurrent Hematologic Tumors

Allogeneic γ9δ2 T Cells for the Treatment of Recurrent Hematologic Tumors After Allogeneic Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Diseases
• Intervention / Treatment: Biological: allogeneic γ9δ2 T Cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Zoredronic acid

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhu Xiaoyu, Ph.D; Phone Number: +86 15255456091; Email: xiaoyuz@ustc.edu.cn
• Study Contact Backup: Name: Sun Guangyu; Phone Number: +86 13956970687; Email: sunguangyu_vip@foxmail.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230036
      • Recruiting
      • Anhui Provincial Hospital
      • Contact: Zhu Xiaoyu, Ph.D; Phone Number: +86 15255456091; Email: xiaoyuz@ustc.edu.cn
      • Contact: Sun Guangyu; Phone Number: +86 13956970687; Email: sunguangyu_vip@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 12-65 (inclusive)；
2. Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation；

3. 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；
4. No obvious hereditary disease;
5. Normal cardiac function, cardiac ejection index above 55%;
6. 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;
7. Sign informed consent.

Exclusion Criteria:

1. Patients with simple extramedullary recurrence;
2. Pregnant and lactating women;

3. 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.
4. Patients with a history of solid organ transplantation;
5. 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;
6. Patients with systemic autoimmune diseases or primary immunodeficiency;
7. Patients with allergic constitution;
8. Use of systemic steroid drugs;
9. Chronic diseases requiring the use of immunological agents or hormone herapy;
10. Prior treatment with any other immune cells;
11. Participated in similar clinical trials within 30 days;
12. Received radiation therapy within 4 weeks from the time of enrollment;
13. Researchers don't think clinical trials are appropriate for other reasons.

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: Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation; 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

Biological: allogeneic γ9δ2 T Cells; dose escalation (3+3) : dose 1 (5 × 10^7cells/kg) ,dose 2 (1 × 10^8 cells/kg) ,dose 3 (2 × 10^8cells/kg); Drug: Fludarabine; Intravenous fludarabine on days-5 and -4,the infusion dose is adjusted according to the subject's condition; Other Names: Fludarabine Phosphate for Injection; Drug: Cyclophosphamide; Intravenous cyclophosphamide on days -5、-4、and -3, the infusion dose is adjusted according to the subject's condition; Other Names: Cyclophosphamide for Injection; Drug: Zoredronic acid; Intravenous zoredronic acid 50ug/kg 24 hours before cell infusion（or according to the dosage of the instruction）（If applicable）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months
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.	First infusion date of allogeneic γ9δ2 T cells to 14 days end cell infusion
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.	14 days
Recommended phase 2 dose (RP2D)	The recommended dose for phase 2 was determined through phase 1 study	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
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.	12 months
Pharmacokinetics: Persistence of the allogeneic γ9δ2 T cells	Persistence of the allogeneic γ9δ2 T cells assessed by number in peripheral blood.	14 days
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.	14 days

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Zhu Xiaoyu, Ph.D, Director of Hematology Department, Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 6, 2023

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Recurrent hematologic tumors; Allogenic γδT Cell
• Additional Relevant MeSH Terms: Hematologic Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Fludarabine phosphate
• Other Study ID Numbers: QH10103-M-01（0）

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No