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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04107142
Recruitment Status : Unknown
Verified September 2019 by CytoMed Therapeutics Pte Ltd.
Recruitment status was:  Not yet recruiting
First Posted : September 27, 2019
Last Update Posted : September 27, 2019
Sponsor:
Information provided by (Responsible Party):
CytoMed Therapeutics Pte Ltd

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Triple Negative Breast Cancer Sarcoma Nasopharyngeal Carcinoma Prostate Cancer Gastric Cancer Biological: Adoptive Cell Transfer of NKG2DL-targetting Chimeric Antigen Receptor-grafted Gamma Delta T cell Phase 1

Detailed Description:

CTM-N2D-101 is a phase I dose-escalation study to evaluate the safety of CTM-N2D and the feasibility to produce CTM-N2D for three target dose levels between 3x10^8 - 3x10^9 per infusion will be tested. Four doses will be given at an interval of a week into subjects with relapsed or refractory solid tumors.

A typical 3+3 design will be used to determine the safe regimen basing on the incidence of dose-limiting toxicity (DLT). The identified safe regimen will be used for further phase II studies for selected indications.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Sequential Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase I Dose-escalation Trial to Evaluate Haploidentical / Allogeneic Natural Killer Group 2D Ligand (NKG2DL)-Targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects With Relapsed or Refractory Solid Tumour
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : March 1, 2021


Arm Intervention/treatment
Experimental: CAR-T Cell Therapy Group

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




Primary Outcome Measures :
  1. Number of Patients with Dose Limiting Toxicity [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. Occurence of adverse events during therapy [ Time Frame: 6 months ]
    A secondary outcome is to observe for the occurence of any adverse events (AEs) and serious adverse events (SAEs) during 4 cycles of treatment and the week after treatment

  2. Observation of clinical efficacy [ Time Frame: 6 months to 2 years ]
    A secondary outcome is to observe for the occurrence of objective clinical response at d31, M3, M6, M9, M12, M18 and M24 after the start of 1st cycle of treatment (assessed according to RECIST criteria, version 1.1)

  3. Observation for progression-free survival [ Time Frame: up to 2 years ]
    A secondary outcome is to observe for progression-free survival (PFS) and after the start of 1st cycle of treatment

  4. Observation for duration of response [ Time Frame: Up to 2 years ]
    A secondary outcome is to observe the duration of response in patients with objective response up to M24, After the start of 1st cycle of treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).

Cancer-specific inclusion criteria of subject:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04107142


Contacts
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Contact: Peter Choo +65 9732 8844 peterchoo@cytomed.sg
Contact: Wee Kiat Tan +65 9816 9085 weekiattan@cytomed.sg

Locations
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Malaysia
Landmark Medical Centre
Johor Bahru, Johor, Malaysia, 80000
Contact: Lucas Luk       drlucas@landmarkmedical.com.my   
Contact: Wee Kiat Tan       weekiattan@cytomed.sg   
Principal Investigator: Lucas Luk         
Sponsors and Collaborators
CytoMed Therapeutics Pte Ltd
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Responsible Party: CytoMed Therapeutics Pte Ltd
ClinicalTrials.gov Identifier: NCT04107142    
Other Study ID Numbers: CTM-N2D
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CytoMed Therapeutics Pte Ltd:
NKG2D
gamma
delta
T cell
CAR
chimeric antigen receptor
solid tumour
cancer immunotherapy
adoptive cell transfer
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Nasopharyngeal Carcinoma
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Breast Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases