AML, AdultPhase 1EPITHINKNCT03612739
EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2
A Phase 1 study testing NKR-2 CAR-T Cells in people with AML, Adult and Myelodysplastic Syndromes, run by Celyad Oncology SA.
Trial summary
This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML, Adult, Myelodysplastic Syndromes
- What is being tested?
- NKR-2 CAR-T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2018to Aug 2021
- 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
- The patients may not be included in the study if one or more of the following criteria is met:
- Patients with confirmed or history of tumor involvement in the central nervous system (CNS).
- Patients who have received any prior AML/MDS therapy (investigational agent or not).
- Note: Patients are authorized to receive hydroxyurea according to specific conditions as detailed in Section 6.4.
- Patients who are planned to receive, concurrently receiving or have received any investigational agent within 3 weeks before the planned day for the first NKR-2 administration.
- Patients who are under systemic immunosuppressive drugs, unless specific cases authorized per protocol (see Section 6.4).
Show all 24Show fewer
- Presence of any indwelling catheter or drain (e.g., percutaneous nephrostomy tube, indwelling foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter) may be permissible unless they have a catheter-associated infection that cannot be cleared with antibiotics. Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath, peripherally inserted central catheter, or Hickman catheter are permitted.
- Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration. Note: Placement of vascular access device is authorized until 10 days before the planned day for the first NKR-2 administration.
- Patients who have received a live vaccine ≤ 6 weeks prior to each NKR-2 administration.
- Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder including, but not limited to evidence of active pneumonitis on screening chest imaging, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia history (or evidenced after the electrocardiogram planned at screening) and/or pronounced disturbances of the electrical conduction system of the heart, or significant thromboembolic events.
- Patients with significant disorder of coagulation or receiving treatment with warfarin derivatives or heparin.
- Note: Patients receiving systemic individual doses of low molecular weight heparin outside 24 hours prior to each NKR-2 administration are eligible.
- Patients who have active infections including, but not limited to viral, bacterial or fungal infections necessitating use of antibiotics/antivirals/antifungal treatment (prophylaxis is acceptable).
- Patients who are known to be positive or screened positive for hepatitis B (HBsAg positive) or C (anti-HCV positive).
- Patients who are known to be positive or screened positive for the human immunodeficiency virus (HIV).
- Patients with a family history of congenital or hereditary immunodeficiency.
- Patients with a history of allergic reactions or hypersensitivity attributed to Human serum albumin, Plasma-lyte A.
- Patients with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis and/or active or acute exacerbation of chronic obstructive pulmonary disease (COPD).
- Patients on supplemental home oxygen.
- Patients with a history of any autoimmune disease including, but not limited to inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g.,Wegener's granulomatosis), CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis). Patients with Graves disease and vitiligo will be allowed.
- Patients with a history of a malignancy other than the one evaluated 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 1 year, and
- Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers).
- Patients with psychiatric/social situations or addictive disorders that may compromise the ability of the patients to give informed consent or to comply with the study procedures.
About this study
Official title: An Open-label, Phase I Study to Assess the Safety of NKR-2 Treatment Administered Concurrently With 5-azacytidine in Treatment-naïve Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients Not Candidates for Intensive Therapy
This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation.
This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.
The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-2 administration, the overall study duration will be 15 years after first NKR-2 administration.
Read the detailed description
This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive induction chemotherapy. The treatment consists in six consecutive cycles of AZA, administered at days
- to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5. This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD. The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-
- administration, the overall study duration will be 15 years after first NKR-
2 administration. Patients will be asked to complete a total of 54 visits during the treatment administration phase, and 5 visits during the treatment follow-up phase. During the LTSFU, yearly visits will be scheduled (up to Visit Y15).
- Conditions
- AML, Adult, Myelodysplastic Syndromes
- Being tested
- NKR-2 CAR-T Cells
- Keywords
- CAR-T Cells, NKR-2, AML, Epigenetic drug therapy
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKR-2 CAR-T CellsBiological
Also called 5-azacytidine (AZA)
The treatment consists in six consecutive cycles of AZA, administered at days
1 to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 5-azacytidine + 1x10^8 NKR-2 CAR-T Cells Receives: Biological: NKR-2 CAR-T Cells |
| Cohort 2 | Experimental | 5-azacytidine + 3x10^8 NKR-2 CAR-T Cells Receives: Biological: NKR-2 CAR-T Cells |
| Cohort 3 | Experimental | 5-azacytidine + 1x10^9 NKR-2 CAR-T Cells Receives: Biological: NKR-2 CAR-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence of Dose Limiting toxicities (DLT) during the study treatment until 6 months after initial treatment.
The occurrence of DLTs during the study treatment phase (up to month 6)
Measured: From Day 1 until the 6 month study visit
Secondary outcomes (14)
Additional Safety Endpoint: the occurrence of Adverse Events and Serious Adverse Events and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow-up.
The occurrence of AEs and SAES and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow up (Month 24).
Measured: Study enrollment until the 24 month study visit.
Overall Survival (OS) Follow-Up
The overall survival (OS), will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.
Measured: Study enrollment until the 24 month study visit.
Relapse-Free Survival (RFS) Follow-Up
The Relapse Free Survival (RFS),patients that do not have an event of Progressive disease, will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.
Measured: Study enrollment until the 24 month study visit.
Event Free Survival (EFS) Follow-Up
The Event Free Survival (EFS), will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.
Measured: Study enrollment until the 24 month study visit.
First Objective Clinical Response
The objective clinical response rate (ORR) post the first NKR-2 administration will be evaluated via bone marrow biopsy and aspirate analysis for disease status.
Measured: Study enrollment until the 24 month study visit.
Duration of First Objective Clinical Response
The duration of response, for patients that achieve complete response or partial response post the first NKR-2 administration will be evaluated for all patients that receive at least the first dose of NKR-2 infusion.
Measured: Study enrollment until the 24 month study visit.
Second Overall Clinical Response
The objective clinical response rate (ORR) post retreatment with NKR-2 administration will be evaluated via bone marrow biopsy and aspirate analysis for disease status.
Measured: Study enrollment until the 24 month study visit.
Duration of Second Overall Clinical Response
The duration of response, for patients that achieve complete response or partial response post the first NKR-2 administration.
Measured: Study enrollment until the 24 month study visit.
Cumulative Incidence of Relapse
The cumulative incidence of relapse (CIR), will be evaluated for all patients that are treated with at least one administration of NKR-2
Measured: Study enrollment until the 24 month study visit.
Cumulative Incidence of Death
The cumulative incidence of Death (CID), will be evaluated for all patients that are treated with at least one administration of NKR-2
Measured: Study enrollment until the 24 month study visit.
Non-relapse Mortality Rate (NMR)
The non-relapse mortality rate (NMR), will be evaluated for all patients that are treated with at least one administration of NKR-2
Measured: Study enrollment until the 24 month study visit.
AML Incidence of Response
For AML patients: the incidence of CR, CRMRD-, CRi, MLFS, PR, or SD post NKR-2 administrations until the end of the treatment follow-up (till 24 months after first NKR-2 treatment administration),
Measured: Study enrollment until the 24 month study visit.
MDS Incidence of Response
For MDS patients: the incidence of CR, PR, marrow CR, cytogenic response, hematologic improvement or SD post NKR-2 administrations until the end of the treatment follow-up (till 24 months after first NKR-2 treatment administration)
Measured: Study enrollment until the 24 month study visit.
Allogeneic Bone Marrow Transplant
The number of patients deemed eligible for an allogeneic stem cell transplantation at screening based on aged and comorbidities by the Investigator who are able to achieve this outcome with investigational treatment.
Measured: Study enrollment until the 24 month study visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study startDec 2018 (estimated)
- Primary completionMay 2019 (estimated)
- Study completionAug 2021 (estimated)
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AML, AdultStudies 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation. This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celyad Oncology SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frederic Lehmann, MD, Study director, Celyad SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03612739
- Sponsor's protocol ID
- CYAD-N2T-006
- Acronym
- EPITHINK
- Status last verified
- Nov 2018
- First submitted
- 20 Jul 2018
- Last updated
- 29 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase I Study to Assess the Safety of NKR-2 Treatment Administered Concurrently With 5-azacytidine in Treatment-naïve Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients Not Candidates for Intensive Therapy
- ClinicalTrials.gov ID
- NCT03612739
- Acronym / sponsor ID
- EPITHINK / CYAD-N2T-006
- Conditions
- AML, Adult, Myelodysplastic Syndromes
- Keywords
- CAR-T Cells, NKR-2, AML, Epigenetic drug therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Celyad Oncology SAIndustry (pharma, biotech, devices)
- Study start
- Dec 2018 (estimated)
- Primary completion
- May 2019 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 2 Aug 2018 (actual)
- 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 open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation.
This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.
The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-2 administration, the overall study duration will be 15 years after first NKR-2 administration.
Detailed description
This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive induction chemotherapy. The treatment consists in six consecutive cycles of AZA, administered at days
- to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5. This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD. The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-
- administration, the overall study duration will be 15 years after first NKR-
2 administration. Patients will be asked to complete a total of 54 visits during the treatment administration phase, and 5 visits during the treatment follow-up phase. During the LTSFU, yearly visits will be scheduled (up to Visit Y15).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation. This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: NKR-2 CAR-T Cells5-azacytidine + 1x10^8 NKR-2 CAR-T Cells |
| Cohort 2 | Experimental | Biological: NKR-2 CAR-T Cells5-azacytidine + 3x10^8 NKR-2 CAR-T Cells |
| Cohort 3 | Experimental | Biological: NKR-2 CAR-T Cells5-azacytidine + 1x10^9 NKR-2 CAR-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 (24 listed)
- The patients may not be included in the study if one or more of the following criteria is met:
- Patients with confirmed or history of tumor involvement in the central nervous system (CNS).
- Patients who have received any prior AML/MDS therapy (investigational agent or not).
- Note: Patients are authorized to receive hydroxyurea according to specific conditions as detailed in Section 6.4.
- Patients who are planned to receive, concurrently receiving or have received any investigational agent within 3 weeks before the planned day for the first NKR-2 administration.
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 |
|---|---|---|
| NKR-2 CAR-T CellsAlso: 5-azacytidine (AZA)The treatment consists in six consecutive cycles of AZA, administered at days 1 to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5. | Biological | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
The occurrence of Dose Limiting toxicities (DLT) during the study treatment until 6 months after initial treatment.
Time frame: From Day 1 until the 6 month study visit
The occurrence of DLTs during the study treatment phase (up to month 6)
14 secondary outcomes
Additional Safety Endpoint: the occurrence of Adverse Events and Serious Adverse Events and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow-up.
Time frame: Study enrollment until the 24 month study visit.
Overall Survival (OS) Follow-Up
Time frame: Study enrollment until the 24 month study visit.
Relapse-Free Survival (RFS) Follow-Up
Time frame: Study enrollment until the 24 month study visit.
Event Free Survival (EFS) Follow-Up
Time frame: Study enrollment until the 24 month study visit.
First Objective Clinical Response
Time frame: Study enrollment until the 24 month study visit.
Duration of First Objective Clinical Response
Time frame: Study enrollment until the 24 month study visit.
Second Overall Clinical Response
Time frame: Study enrollment until the 24 month study visit.
Duration of Second Overall Clinical Response
Time frame: Study enrollment until the 24 month study visit.
Cumulative Incidence of Relapse
Time frame: Study enrollment until the 24 month study visit.
Cumulative Incidence of Death
Time frame: Study enrollment until the 24 month study visit.
Non-relapse Mortality Rate (NMR)
Time frame: Study enrollment until the 24 month study visit.
AML Incidence of Response
Time frame: Study enrollment until the 24 month study visit.
MDS Incidence of Response
Time frame: Study enrollment until the 24 month study visit.
Allogeneic Bone Marrow Transplant
Time frame: Study enrollment until the 24 month study visit.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2019.
- Individual participant dataSharing planned: Undecided
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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.
Frederic Lehmann, MD study director
Celyad SA
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NKR-2 CAR-T Cells in people with AML, Adult and Myelodysplastic Syndromes, run by Celyad Oncology SA.
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 24 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: withdrawn, as of the sponsor's last update on 29 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
The occurrence of Dose Limiting toxicities (DLT) during the study treatment until 6 months after initial treatment. (time frame: From Day 1 until the 6 month study visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Oct 2019.