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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-31

Study Completion Date

2018-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Efficacy of Dendritic Cell Therapy for Myeloid Leukemia and Myeloma

NCT00965224

Acute Myeloid Leukemia Chronic Myeloid Leukemia Multiple Myeloma

COMPLETED PHASE2

Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant

NCT04815356

Hairy Cell Leukemia Hairy Cell Leukemia Variant

RECRUITING PHASE1

Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission

NCT01096602

Acute Myelogenous Leukemia AML

COMPLETED PHASE2

DC Vaccination in CML

NCT02543749

Myeloid Leukemia, Chronic

TERMINATED PHASE1/PHASE2

NKG2D CAR-T(KD-025) in the Treatment of Advanced NKG2DL+ Solid Tumors

NCT06509490

Safety Issues

RECRUITING NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 with progressive disease.

In this study, the participant's white blood cells (T-cells) will be collected and modified such that the T-cells are able to recognize specific molecules (called NKG2D-ligands), that are expressed on the surface of cancer cells in these diseases. This modification is a genetic change to the T-cells. The modified T cells, called CM-CS1 T-cells, are then given back to the participant by a single intravenous infusion. In this study, participants will not receive any chemotherapy prior to infusion of the CM-CS1 T-cells.

The study will evaluate whether it is safe and feasible to administer CM-CS1 T-cells to participants with AML/MDS-RAEB and multiple myeloma. It will also evaluate whether the CM-CS1 T-cells have a beneficial effect against the cancer cells. Another goal of the study is to learn more about the persistence and function of the CM-CS1 T-cells in the body.

Participants will be followed very closely during the first month after infusion. They are required to remain within 50 miles of Brigham and Women's Hospital (Boston, MA) for 10 days after the infusion and will be followed three times per week for the first 21 days and at day 28. Subsequently, participants will be followed monthly until 6 months after infusion, every 3 months until 15 months after infusion and at 24 months after infusion. Because this study involves gene transfer, participants will be followed yearly for up to 15 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Myeloid Leukemia Myelodysplastic Syndrome Multiple Myeloma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CM-CS1 T-cell infusion

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

Group Type EXPERIMENTAL

CM-CS1 T-cell infusion

Intervention Type BIOLOGICAL

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CM-CS1 T-cell infusion

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

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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:

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 \> 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
2. Platelets \>20,000/mcL. Subjects may receive platelet transfusions, if clinically indicated, in accordance with institutional guidelines.
3. Total bilirubin ≤2.0 × institutional upper limit of normal. (Except patients with known Gilbert's syndrome)
4. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
5. 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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No