Haplo / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells for Relapsed or Refractory Solid Tumour

NCT04107142 | Unknown Phase 1

• 1 other identifier: CTM-N2D
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is an open-label, single-centre, dose escalation, phase I study designed to investigate the safety and tolerability of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects with Relapsed or Refractory Solid Tumour. The study objectives of this phase I study are to determine the safety, activity and the safe dose of haploidentical or allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells given four times weekly in patients with relapsed or refractory solid tumors of different types.

Conditions

Colorectal Cancer; Triple Negative Breast Cancer; Sarcoma; Nasopharyngeal Carcinoma; Prostate Cancer; Gastric Cancer

Keywords

NKG2D; gamma; delta; T cell; CAR; chimeric antigen receptor; solid tumour; cancer immunotherapy; adoptive cell transfer

Outcome Measures

Primary Outcomes (1)

• Number of Patients with Dose Limiting Toxicity

  The primary endpoint of this dose-escalation study will be the occurrence of dose-limiting toxicities (DLTs) during 4 cycles of treatment and the week after treatment.

  6 months

Secondary Outcomes (4)

• Occurence of adverse events during therapy

  6 months

• Observation of clinical efficacy

  6 months to 2 years

• Observation for progression-free survival

  up to 2 years

• Observation for duration of response

  Up to 2 years

Study Arms (1)

CAR-T Cell Therapy Group

EXPERIMENTAL

One arm study consisting of "3 + 3" dose escalation study design ranging from 3 x 10\^8 - 3 x 10\^9 cells CAR-γδ T cell. Each cycle of therapy will consist of 4 intravenous infusions, given 7 days apart.

Biological: Adoptive Cell Transfer of NKG2DL-targetting Chimeric Antigen Receptor-grafted Gamma Delta T cell

Interventions

Adoptive Cell Transfer of NKG2DL-targetting Chimeric Antigen Receptor-grafted Gamma Delta T cell BIOLOGICAL

Adoptive Cell Transfer of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells (CTM-N2D)

CAR-T Cell Therapy Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥18 years old.
• Patient with specific cancer indications (see below).
• Disease must be measurable according to the corresponding guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2.
• Patient with adequate bone marrow reserve (Haemoglobin ≥10g/dl, Absolute Neutrophil Count (ANC)≥1,500/mm3, Platelet≥100,000/mm3), hepatic function (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \< 3x upper limit of normal), renal function (serum creatinine \< 120 µmol/L) and cardiac function (Left ventricular ejection fraction of ≥50% by ECHO).
• Patient must already have a previous tumour biopsy to confirm the disease.
• Patient must agree to sign the informed consent form (ICF).
• Colorectal cancer: A documented metastatic colorectal adenocarcinoma and having received, being intolerant to or being unfit for at least two prior standard cancer therapy regimens as part of their primary treatment regimen or part of their treatment for management of recurrent/persistent disease.
• Breast cancer: A metastatic triple-negative breast cancer and having received at least two prior cancer therapy regimens as part of their treatment for management of recurrent/persistent disease.
• Sarcoma, nasopharyngeal cancer, prostate cancer or gastric cancer: A metastatic cancer and having received at least two prior cancer therapy regimens as part of their treatment for management of recurrent/persistent disease.

You may not qualify if:

• Patients with a tumour metastasis in the central nervous system.
• Patients who receive or are to receive any investigational product within the 4 weeks before the planned day for the first CTM-N2D administration.
• Patients who receive or are to receive chemotherapy within the 8 weeks before the planned day for the first CTM-N2D administration.
• Patients who are planned to receive concurrent growth factor, systemic steroid or other immunosuppressive therapy or cytotoxic agent.
• Patients who underwent major surgery within 4 weeks before the planned day for the first CTM-N2D administration.
• Patients who have active infections necessitating the use of antibiotics/antivirals treatment.
• Patients with a history of autoimmune disease.

Sponsors & Collaborators

• CytoMed Therapeutics Pte Ltd: lead

Study Sites (1)

Landmark Medical Centre

Johor Bahru, Johor, 80000, Malaysia

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Triple Negative Breast Neoplasms; Sarcoma; Nasopharyngeal Carcinoma; Prostatic Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Stomach Diseases

Central Study Contacts

Peter Choo

CONTACT

+65 9732 8844; peterchoo@cytomed.sg

Wee Kiat Tan

CONTACT

+65 9816 9085; weekiattan@cytomed.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consisT of "3 + 3" dose escalation study design with 3 distinct dose level. The first dose level will be at 3 x 10\^8 chimeric antigen receptor (CAR) grafted γδ T cells per infusion. The second dose level will be at 1 x 10\^9 CAR-γδT cells per infusion. The third dose level will be increased to 3 x 10\^9 cells CAR-γδT cells. Each cycle of therapy will consist of 4 intravenous infusions, given 7 days apart.

Study Record Dates

• First Submitted: September 21, 2019
• First Posted: September 27, 2019
• Study Start: December 1, 2019
• Primary Completion: September 1, 2020
• Study Completion: March 1, 2021
• Last Updated: September 27, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)