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

NCT02203825 | Completed Phase 1 DMC

• 2 other identifiers: CM-14-0015R44HL099217-03
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 feasibility of administering a single intravenous dose of CM-CS1 CAR T-cells to patients with AML, MDS-RAEB and Multiple Myeloma.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Multiple Myeloma

Keywords

Acute Myeloid Leukemia; NKG2D; Multiple Myeloma; Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Safety and feasibility of intravenous administration of CM-CS1 T-cells.

  Safety will be defined by the occurence of study-related serious and non-serious adverse events. Feasibility will be defined by the frequency of subjects enrolled who do not receive CM-CS1 T-cells.

  24 months

Secondary Outcomes (1)

• Clinical and biologic responses

  24 months

Study Arms (1)

CM-CS1 T-cell infusion

EXPERIMENTAL

The treatment will consist of a single infusion of CM-CS1 cells. The following dose levels will be evaluated: Cohort 1: 1x 10\^6 CM-CS1 T-cells Cohort 2: 3x 10\^6 CM-CS1 T-cells Cohort 3: 1x 10\^7 CM-CS1 T-cells Cohort 4: 3x 10\^7 CM-CS1 T-cells

Biological: CM-CS1 T-cell infusion

Interventions

CM-CS1 T-cell infusion BIOLOGICAL

Each patient will receive a single dose of CM-CS1 T-cells by intravenous infusion.

CM-CS1 T-cell infusion

Eligibility Criteria

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celyad Oncology SA: lead
• Dana-Farber Cancer Institute: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Murad JM, Baumeister SH, Werner L, Daley H, Trebeden-Negre H, Reder J, Sentman CL, Gilham D, Lehmann F, Snykers S, Sentman ML, Wade T, Schmucker A, Fanger MW, Dranoff G, Ritz J, Nikiforow S. Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy. Cytotherapy. 2018 Jul;20(7):952-963. doi: 10.1016/j.jcyt.2018.05.001. Epub 2018 Jun 29.

  PMID: 30180944 DERIVED

Related Links

• Sponsor

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Multiple Myeloma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sarah Nikiforow, MD; PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2014
• First Posted: July 30, 2014
• Study Start: March 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: June 1, 2018

Record last verified: 2018-05

Locations

US (1)