Status:
COMPLETED
Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands
Lead Sponsor:
Celyad Oncology SA
Collaborating Sponsors:
Dana-Farber Cancer Institute
National Heart, Lung, and Blood Institute (NHLBI)
Conditions:
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This Phase I clinical trial is evaluating chimeric-antigen receptor (CAR) T-cells (CM-CS1 T cells) which recognize NKG2D-ligands on the surface of cancer cells. This study evaluates the safety and fea...
Detailed Description
This is a study for patients with AML or MDS-RAEB that is not in remission and for which there are no reasonable standard treatment options and for patients with relapsed/refractory multiple myeloma w...
Eligibility Criteria
Inclusion
- 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.
- Pathological confirmation of 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:
- Pathological confirmation of 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:
- Total bilirubin ≤2.0 × institutional upper limit of normal (Except for subjects with known Gilbert's syndrome)
- AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
- 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:
- Serum M-protein \>0.5g/dl
- Urine M-protein \> 200mg/24hr
- Serum FLC assay: involved FLC level \> 10mg/dl with abnormal serum FLC ratio
- 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:
- Absolute neutrophil count \> 500/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
- Platelets \>20,000/mcL. Subjects may receive platelet transfusions, if clinically indicated, in accordance with institutional guidelines.
- Total bilirubin ≤2.0 × institutional upper limit of normal. (Except patients with known Gilbert's syndrome)
- AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
- 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:
- Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 2 years are not excluded.
- 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.
Exclusion
Key Trial Info
Start Date :
March 1 2015
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2018
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT02203825
Start Date
March 1 2015
End Date
March 1 2018
Last Update
June 1 2018
Active Locations (1)
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1
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215