Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands


In this Phase I clinical trial, the investigators will be evaluating if it is safe and feasible to give T cells expressing a chimeric NKG2D receptor to patients. We will also look to see if the T cells have a beneficial effect against tumors expressing NKG2D ligands and learn more about the persistence and the function of the cells in the body.
SparkCures ID 640
Trial Phase Phase 1
Enrollment 21 Patients
  • T Cells
Trial Sponsors
  • Celyad Therapeutics
Trial Collaborators
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Dana-Farber Cancer Institute (Main)
NCT Identifier


Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

General eligibility criteria:

  • ECOG performance status 0 or 1.Patients with multiple myeloma who have an ECOG performance status of 2 based on peripheral neuropathy from prior therapies are eligible.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Histologically confirmed AML, MDS-RAEB or Multiple myeloma.
  • Agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CM-CS1 CART-cell administration.
  • Ability to adhere with the study visit schedule and other protocol procedures.
  • Willingness to remain within a 50 mile radius of Brigham Women's Hospital during the initial 10 days following CM-CS1 infusion

Disease specific eligibility criteria for patients with AML, MDS-RAEB:

  • Histologically confirmed AML, MDS-RAEB according to WHO classification (CMML is excluded) that is not in remission (defined as >5% blasts in bone marrow or peripheral blood) and for which there are no reasonable standard treatment options.
  • No known or suspected CNS disease. A neurologic exam is required and signs or symptoms suggestive of potential CNS disease require CNS imaging.
  • Disease status deemed not to require additional therapy for at least 4 weeks from enrollment.
  • Life expectancy of greater than 4 weeks.
  • Participants must have satisfactory organ function as defined below:
    1. Total bilirubin ≤2.0 × institutional upper limit of normal (Except for subjects with known Gilbert's syndrome)
    2. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
    3. Creatinine ≤ 2.0 mg/dL

Disease specific eligibility criteria for patients with multiple myeloma:

  • Diagnosis of active multiple myeloma according to the International Myeloma Working Group diagnostic criteria.
  • Relapsed or relapsed/refractory multiple myeloma with progressive disease
  • Presence of measurable disease as defined as one or more of the following:
    1. Serum M-protein >0.5g/dl
    2. Urine M-protein > 200mg/24hr
    3. Serum FLC assay: involved FLC level > 10mg/dl with abnormal serum FLC ratio
    4. Measurable plasmocytoma in non-secretory patients.
  • Previous treatment with both an immunomodulator and a proteosome inhibitor therapy
  • Life expectancy of greater than 12 weeks
  • No known or suspected CNS involvement. A neurologic exam is required and signs or symptoms of potential CNS involvement require CNS imaging. Peripheral neuropathy is acceptable.
  • Participants must have satisfactory organ and marrow function as defined below:
    1. Absolute neutrophil count ≥1,000/mcL. Screening ANC should be independent of G-CSF and GM-CSF support for at least 1 week and of pegylated G-CSF for at least 2 weeks
    2. Platelets ≥60,000/mcL. Subjects may receive platelet transfusions, if clinically indicated, in accordance with institutional guidelines.
    3. Hemoglobin ≥8.0g/dL. Screening hemoglobin should be independent of red blood cell transfusions for at least 2 weeks. Subjects may receive red blood cell transfusions, if clinically indicated, in accordance with institutional guidelines
    4. Total bilirubin ≤2.0 × institutional upper limit of normal. (Except patients with known Gilbert's syndrome)
    5. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
    6. Creatinine ≤ 2.0 mg/dL

Exclusion Criteria:

  • Participants who have received chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
  • Concurrent systemic steroid or other immunosuppressive therapy.
  • Participants who are concurrently receiving any other investigational agents, or have received another investigational agent within 3 weeks before enrollment.
  • Participants who have received prior allogeneic stem cell transplantation, gene therapy, or adoptive T-cell therapy.
  • Active infections necessitating use of treatment antibiotics/antivirals during the screening period (prophylaxis is acceptable) or evidence of an active communicable infectious disease.
  • Participants who underwent major surgery within 4 weeks before day 0 of planned CM-CS1 T-cell infusion (this does not include placement of vascular access device or tumor biopsies).
  • Participants with any known history of primary immunodeficiency.
  • History of allergic reactions or hypersensitivity attributed to Human serum albumin or Plasma-lyte A.
  • Uncontrolled intercurrent illness or serious uncontrolled medical disorder
  • Pregnancy or breastfeeding
  • Known HIV-positive participants are ineligible because the effect of transducing HIV-infected lymphocytes with the chimeric NKG2D- transgene on the disease course is unknown.
  • Clinically relevant active infection including active hepatitis B or C or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study.
  • Active autoimmune disease
  • History of a malignancy other than one of the malignancies in this study with exception of the following circumstances:
    1. Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 2 years are not excluded.
    2. Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are not excluded.
  • Unwillingness to use an effective contraceptive method during the study and at least 4 months after administration of CM-CS1 T-cells unless subject is naturally infertile.

US Trial Locations

Please visit the page for historical site information.

View Centers