Acute Myeloid LeukemiaPhase 1NCT02203825
Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands
A Phase 1 study testing CM-CS1 T-cell infusion in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Celyad Oncology SA at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome, Multiple Myeloma
- What is being tested?
- CM-CS1 T-cell infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia (AML)/Advanced Myelodysplastic Syndrome (MDS-RAEB) and Multiple Myeloma.
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.
Read the 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 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.
- Being tested
- CM-CS1 T-cell infusion
- Keywords
- Acute Myeloid Leukemia, NKG2D, Multiple Myeloma, Cell Therapy
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CM-CS1 T-cell infusionBiological
Each patient will receive a single dose of CM-CS1 T-cells by intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: CM-CS1 T-cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (1)
Clinical and biologic responses
Clinical anti-tumor effect by standard criteria Progression-Free survival Persistence and function of CM-CS1 T-cells
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study startMar 2015
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celyad Oncology SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sarah Nikiforow, MD; PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203825
- Sponsor's protocol ID
- CM-14-001
- Other IDs
- 5R44HL099217-03
- Status last verified
- May 2018
- First submitted
- 25 Jul 2014
- Last updated
- 1 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30180944
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia (AML)/Advanced Myelodysplastic Syndrome (MDS-RAEB) and Multiple Myeloma.
- ClinicalTrials.gov ID
- NCT02203825
- Acronym / sponsor ID
- CM-14-001
- Keywords
- Acute Myeloid Leukemia, NKG2D, Multiple Myeloma, Cell Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Celyad Oncology SAIndustry (pharma, biotech, devices)
- Collaborators
- Dana-Farber Cancer Institute, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2015
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 30 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CM-CS1 T-cell infusion | Experimental | Biological: CM-CS1 T-cell infusionThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CM-CS1 T-cell infusionEach patient will receive a single dose of CM-CS1 T-cells by intravenous infusion. | Biological | CM-CS1 T-cell infusion |
Primary outcome
Safety and feasibility of intravenous administration of CM-CS1 T-cells.
Time frame: 24 months
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.
1 secondary outcome
Clinical and biologic responses
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2018.
- Derived from this study: PubMed 30180944Murad 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.
- SponsorLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Nikiforow, MD; PhD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CM-CS1 T-cell infusion in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Celyad Oncology SA at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and feasibility of intravenous administration of CM-CS1 T-cells. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02203825, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2018.