Authorised Human Pharmacology (Phase I)- First administration to humans Sarcoma

Trial to evaluate CAR-T NKG2D CAR cell infusions in patients with advanced sarcoma

EU CTIS ID: 2024-513514-35-00

What this study is testing

To determine the safety and feasibility of a Phase I Clinical Trial on administering escalating doses of NKG2D-CAR memory T cells in children and young adults with advanced sarcoma. To analyze the efficacy of NKGD2-CAR memory T cells in patients’ tumor volume after therapy.

  • Human Pharmacology (Phase I)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Age: ≤ 40 years at the time of recurrence or progression with any type of sarcoma that has recurred or not responded to standard therapy and is deemed incurable by standard therapy.
  • Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
  • Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the infusion. Male partner should use a condom.
  • Positive NKG2DL expression in sarcoma samples. Ideally, they should have centralized histological verification of NKG2DL expression in sarcoma samples (positive expression is defined as at least 2+ expression (0-4+ scale) in >50 percent of the tumor cells using anti-MICA and or anti-ULBP2). Patients will undergo biopsy following enrollment to obtain tissue to assess NKG2DL expression, with the following restrictions: o If the patient does not have an adequate accessible tumor for biopsy (at least 1 cm diameter). o Procedures employed to acquire biopsies for tumor lysates will be limited to percutaneous needle or core biopsies, thoracoscopic excision or open biopsies of readily accessible lesions. Pulmonary lesions may be biopsied but extensive surgery such as thoracotomy or laparotomy should not be employed. o Patients who require biopsy should not be enrolled if in the opinion of the principal investigator (PI), the tumor site places the patient at substantial related risk from the biopsy procedure. In patients that fulfill any of these restrictions, when adequate archived tissue is available, this may be utilized to assess NKG2DL expression.
  • Patients must have either measurable or evaluable tumor.
  • The tumor must be accessible for intralesional administration of CAR T cells (only in ARM B).

You likely can't join if

  • Enrolled in another treatment protocol.
  • Evidence of untreated and active infection or clinically significant systemic illness: o Cardiac disorder defined as LVFE < 45 % determined by ECHO. o Human Immunodeficiency Virus (HIV) positive test. o Presence of active or prior CMV, EBV, hepatitis B or C as indicated by serology. o Any significant pulmonary, hepatic or other organ dysfunction.
  • Chronic corticosteroid dependence (except replacement therapy).
  • Evidence of any toxicity grade ≥ 4 (according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0).
  • Pregnant or lactating women.
  • Medical history of epilepsy.
See the full eligibility criteria
Who can join
  • Age: ≤ 40 years at the time of recurrence or progression with any type of sarcoma that has recurred or not responded to standard therapy and is deemed incurable by standard therapy.
  • Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
  • Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the infusion. Male partner should use a condom.
  • Positive NKG2DL expression in sarcoma samples. Ideally, they should have centralized histological verification of NKG2DL expression in sarcoma samples (positive expression is defined as at least 2+ expression (0-4+ scale) in >50 percent of the tumor cells using anti-MICA and or anti-ULBP2). Patients will undergo biopsy following enrollment to obtain tissue to assess NKG2DL expression, with the following restrictions: o If the patient does not have an adequate accessible tumor for biopsy (at least 1 cm diameter). o Procedures employed to acquire biopsies for tumor lysates will be limited to percutaneous needle or core biopsies, thoracoscopic excision or open biopsies of readily accessible lesions. Pulmonary lesions may be biopsied but extensive surgery such as thoracotomy or laparotomy should not be employed. o Patients who require biopsy should not be enrolled if in the opinion of the principal investigator (PI), the tumor site places the patient at substantial related risk from the biopsy procedure. In patients that fulfill any of these restrictions, when adequate archived tissue is available, this may be utilized to assess NKG2DL expression.
  • Patients must have either measurable or evaluable tumor.
  • The tumor must be accessible for intralesional administration of CAR T cells (only in ARM B).
  • Life expectancy of at least 10 weeks in opinion of the principal investigator (PI).
  • Lansky (age <16 years) or Karnofsky (age >=16 years) score of 50 or greater.
  • Patients must have recovered from the acute toxic effects of all prior anticancer therapy (including chemotherapy and radiotherapy).
  • Adequate bone marrow function defined by an absolute neutrophil count (ANC) of >/= 1.000/μL, platelet count of >/= 30.000/μL and hemoglobin of >/= 9.0 g/dl, and absence of a regular red blood cell and platelet transfusion requirement.
  • Patients should have a normal hepatic function with a total bilirubin <2 times the upper limit of normal and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) < 2 times the upper limit of normal, and adequate renal function as defined by a serum creatinine ≤ 1.5 upper limit of normal.
What rules you out
  • Enrolled in another treatment protocol.
  • Evidence of untreated and active infection or clinically significant systemic illness: o Cardiac disorder defined as LVFE < 45 % determined by ECHO. o Human Immunodeficiency Virus (HIV) positive test. o Presence of active or prior CMV, EBV, hepatitis B or C as indicated by serology. o Any significant pulmonary, hepatic or other organ dysfunction.
  • Chronic corticosteroid dependence (except replacement therapy).
  • Evidence of any toxicity grade ≥ 4 (according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0).
  • Pregnant or lactating women.
  • Medical history of epilepsy.
  • Any other condition that, in the opinion of the PI, may interfere with the efficacy and/or safety evaluation of the trial.

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 0-17 years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.