Acute Myeloid Leukemia/Myelodysplastic SyndromePhase 1/2THINKNCT03018405
A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications
A Phase 1/2 study testing NKR-2 cells in people with Acute Myeloid Leukemia/Myelodysplastic Syndrome and Multiple Myeloma (MM), run by Celyad Oncology SA at 5 sites in 2 countries.
Trial summary
THINK (THerapeutic Immunotherapy with NKR-2) is a multinational (EU/US) open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 cells in seven refractory cancers, including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic… 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 (MM)
- What is being tested?
- NKR-2 cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Dec 2016to Aug 2021
- Phase
- Phase 1/2
- 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
Main inclusion criteria are:
- Men or women ≥ 18 years old at the time of signing the ICF,
- Patient with a CRC, epithelial ovarian cell or fallopian tube carcinoma, urothelial carcinoma, TNBC, pancreatic cancer, AML/MDS or MM,
- Disease must be measurable according to the corresponding guidelines,
- Patient with an ECOG performance status 0 or 1, and AML patients with anemia resulting in an ECOG performance status of 2,
- Patient with adequate bone marrow reserve, hepatic and renal functions.
- Patients must have sufficient pulmonary functions with a Forced Expiratory Volume in the first second (FEV-1)/Forced Vital Capacity (FVC) ≥ 0.7 with FEV-1 ≥ 50% predicted.
Main exclusion criteria are:
- Patient with a tumor metastasis in the central nervous system,
- Patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis (except hydroxyurea for AML patients),
- Patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first NKR-2 administration (except hydroxyurea for AML patients),
- Patient is under systemic immunosuppressive drugs, unless specific cases authorized per protocol,
- Patients who have received other cell therapies,
- Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration.
- Patient cannot present with history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis and/or active or acute exacerbation of chronic obstructive pulmonary disease (COPD).
Detailed disease specific criteria exist and can be discussed with contacts listed below.
Trial locations and contacts
5 sites in 2 countries.
Amélie Vanneste contact
Anne Flament, MD contact
5 sites in 2 countries
Belgium3 sites, 3 recruiting
- Recruiting
Study site
Brussels, 1200
Anne Moxhon, +32 2 764.42.17, anne.moxhon@uclouvain.be
- Recruiting
Study site
Brussels
Michel Dubuisson, +32 (0) 2 541 31 79, michel.dubuisson@bordet.be
- Recruiting
Study site
Ghent
Jonas Segaert, 32 (0)9 332 4912, jonas.segaert@uzgent.be
Liesbeth Delanghe, Liesbeth.delanghe@uzgent.be
United States2 sites, 2 recruiting
- Recruiting
Study site
Buffalo, New York, 14263
Amy Whitworth, 877-275-7724, ASKRPCI@roswellpark.org
- Recruiting
Study site
Tampa, Florida, 33612
Jeff Edelman, 813-745-1040, Jeffrey.Edelman@moffitt.org
About this study
Official title: A Multi-national, Open-label, Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Administrations of NKR-2 in Patients With Different Metastatic Tumor Types (THINK - THerapeutic Immunotherapy With NKR-2)
THINK (THerapeutic Immunotherapy with NKR-2) is a multinational (EU/US) open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 cells in seven refractory cancers, including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma).
Read the detailed description
This open-label Phase I study aims at assessing the safety and clinical activity of the NKR-2 treatment administered 3 times with a 2-week interval between each administration in different tumor types. In absence of progressive disease at the first tumor assessment following NKR-2 administratio, the patient will receive a new cycle of 3 administrations maximum with a 2-week interval. The study will contain two consecutive segments: a Phase I dose escalation and a Phase I expansion segment.
The Phase I dose escalation segment will include 2 arms, one in solid tumors and one in hematological tumors. The dose escalation design will include 3 dose levels: The dose escalation phase will consist of 3 cohorts (Cohorts 1-3) for the solid tumors, and 3 cohorts (Cohorts 4-6) for the hematological tumors; with each set of 3 cohorts receiving escalating doses of the NKR-2 therapy.
Two additional cohorts will be added in each dose escalation arm with the aim to provide a more intense treatment during the induction treatment. These additional cohorts in both the solid arm (cohort 8-9 - only in CRC) and in the hematological arm of the study (cohort 10-11 - only in AML/MDS) will therefore evaluate a tighter schedule of NKR-2 injections with the three first injections within the induction cycle separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three NKR 2 injections. These cohorts will each enroll 3 patients in case of no DLT. Based on safety and early clinical data from these cohorts, the specific schedule of cohorts 8-11 might be selected for the expansion.
- Being tested
- NKR-2 cells
- Medical subject headings
- GATA2 Deficiency, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKR-2 cellsBiological
Also called NKG2D-CAR construct
In cohorts 1-6, the schedule of administration will be 3 NKR-2 doses administered with a 2-week interval. In absence of progressive disease at the first tumor assessment following NKR-2 administration (on Visit D29 for hematological tumors or on Visit D57 for solid tumors), and according to product availability, the patient will receive a new cycle of 3 administrations maximum with a 2-week interval, at a dose of 1x109 NKR-2 cells per injection, or at the same dose of cycle 1 if it was below 1x109 NKR-2 cells.
Patients in cohorts 8-9 (solid arm) and 10-11 (hematological arm) of first segment will receive 3 treatment doses at 1x109 NKR-2 (cohorts 8 and 10) or 3x109 NKR-2 (cohorts 9 and 11) per injection, with a 1-week interval between each dose. A second cycle of three NKR-2 injections at the same dose as in 1st cycle will be administered 2 weeks after the third NKR-2 injection, and with a 2-week interval between each dose.
| Study group | Role | What they receive |
|---|---|---|
| Hematological tumors | Experimental | The dose escalation arm for hematological tumors will use a 3 +3 design to determine the maximum tolerated dose. Two additional cohorts will be added in this dose escalation arm with the aim to provide a more intense treatment during the induction treatment (cycle 1 of injection). Cohort 10-11 (only in AML/MDS) will evaluate a tighter schedule of NKR-2 injections at 1x109 or potentially 3x109 NKR-2 per injection with the three first injections within the induction cycle (cycle 1) separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three NKR 2 injections. Receives: Biological: NKR-2 cells |
| Solid Tumors | Experimental | The dose escalation arm for solid tumors will use a 3 +3 design to determine the maximum tolerated dose. Two additional cohorts will be added in this dose escalation arm with the aim to provide a more intense treatment during the induction treatment (cycle 1 of injection). Cohort cohort 8-9 ( only in CRC) will evaluate a tighter schedule of NKR-2 injections at 1x109 or potentially 3x109 NKR-2 per injection with the three first injections within the induction cycle (cycle 1) separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three NKR 2 injections. Receives: Biological: NKR-2 cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion
Safety defined by Occurrence of adverse events (AEs) and serious adverse events (SAEs) during the study treatment until 30 days after the last study treatment administration.
Measured: 24 months
Secondary outcomes (1)
Clinical activity of the treatment in each tumor type
Clinical activity of the treatment in each tumor type
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 posted12 Jan 2017 (estimated)
- Study startDec 2016
- Primary completionMay 2021 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia/Myelodysplastic SyndromeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- The maximum number of patients to be enrolled is 146: * 36 in the dose escalation segment (cohorts 1-6, 18 per arm), * 24 in the additional cohorts 8-11 (12 per arm), * 86 patients in the Phase I expansion segment (note that the analysis of this segment will also include a maximum of 12 additional patients from the dose escalation segment).
- Masking
- None (open label)
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Celyad Oncology SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frédéric Lehmann, MD, Principal investigator, Celyad Oncology SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03018405
- Sponsor's protocol ID
- CYAD-N2T-002
- Acronym
- THINK
- Status last verified
- Nov 2018
- First submitted
- 10 Jan 2017
- Last updated
- 19 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Sallman DA, Kerre T, Havelange V, Poire X, Lewalle P, Wang ES, Brayer JB, Davila ML, Moors I, Machiels JP, Awada A, Alcantar-Orozco EM, Borissova R, Braun N, Dheur MS, Gilham DE, Lonez C, Lehmann FF, Flament A. CYAD-01, an autologous NKG2D-based CAR T-cell therapy, in relapsed or refractory acute myeloid leukaemia and myelodysplastic syndromes or multiple myeloma (THINK): haematological cohorts of the dose escalation segment of a phase 1 trial. Lancet Haematol. 2023 Mar;10(3):e191-e202. doi: 10.1016/S2352-3026(22)00378-7. Epub 2023 Feb 7.
PubMed 36764323Lonez C, Verma B, Hendlisz A, Aftimos P, Awada A, Van Den Neste E, Catala G, Machiels JH, Piette F, Brayer JB, Sallman DA, Kerre T, Odunsi K, Davila ML, Gilham DE, Lehmann FF. Study protocol for THINK: a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types. BMJ Open. 2017 Nov 12;7(11):e017075. doi: 10.1136/bmjopen-2017-017075.
PubMed 29133316
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-national, Open-label, Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Administrations of NKR-2 in Patients With Different Metastatic Tumor Types (THINK - THerapeutic Immunotherapy With NKR-2)
- ClinicalTrials.gov ID
- NCT03018405
- Acronym / sponsor ID
- THINK / CYAD-N2T-002
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- Celyad Oncology SAIndustry (pharma, biotech, devices)
- Study start
- Dec 2016
- Primary completion
- May 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 12 Jan 2017 (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.
THINK (THerapeutic Immunotherapy with NKR-2) is a multinational (EU/US) open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 cells in seven refractory cancers, including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma).
Detailed description
This open-label Phase I study aims at assessing the safety and clinical activity of the NKR-2 treatment administered 3 times with a 2-week interval between each administration in different tumor types. In absence of progressive disease at the first tumor assessment following NKR-2 administratio, the patient will receive a new cycle of 3 administrations maximum with a 2-week interval. The study will contain two consecutive segments: a Phase I dose escalation and a Phase I expansion segment.
The Phase I dose escalation segment will include 2 arms, one in solid tumors and one in hematological tumors. The dose escalation design will include 3 dose levels: The dose escalation phase will consist of 3 cohorts (Cohorts 1-3) for the solid tumors, and 3 cohorts (Cohorts 4-6) for the hematological tumors; with each set of 3 cohorts receiving escalating doses of the NKR-2 therapy.
Two additional cohorts will be added in each dose escalation arm with the aim to provide a more intense treatment during the induction treatment. These additional cohorts in both the solid arm (cohort 8-9 - only in CRC) and in the hematological arm of the study (cohort 10-11 - only in AML/MDS) will therefore evaluate a tighter schedule of NKR-2 injections with the three first injections within the induction cycle separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three NKR 2 injections. These cohorts will each enroll 3 patients in case of no DLT. Based on safety and early clinical data from these cohorts, the specific schedule of cohorts 8-11 might be selected for the expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The maximum number of patients to be enrolled is 146: * 36 in the dose escalation segment (cohorts 1-6, 18 per arm), * 24 in the additional cohorts 8-11 (12 per arm), * 86 patients in the Phase I expansion segment (note that the analysis of this segment will also include a maximum of 12 additional patients from the dose escalation segment).
| Arm | Type | Receives |
|---|---|---|
| Hematological tumors | Experimental | Biological: NKR-2 cellsThe dose escalation arm for hematological tumors will use a 3 +3 design to determine the maximum tolerated dose. Two additional cohorts will be added in this dose escalation arm with the aim to provide a more intense treatment during the induction treatment (cycle 1 of injection). Cohort 10-11 (only in AML/MDS) will evaluate a tighter schedule of NKR-2 injections at 1x109 or potentially 3x109 NKR-2 per injection with the three first injections within the induction cycle (cycle 1) separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three NKR 2 injections. |
| Solid Tumors | Experimental | Biological: NKR-2 cellsThe dose escalation arm for solid tumors will use a 3 +3 design to determine the maximum tolerated dose. Two additional cohorts will be added in this dose escalation arm with the aim to provide a more intense treatment during the induction treatment (cycle 1 of injection). Cohort cohort 8-9 ( only in CRC) will evaluate a tighter schedule of NKR-2 injections at 1x109 or potentially 3x109 NKR-2 per injection with the three first injections within the induction cycle (cycle 1) separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three NKR 2 injections. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 cellsAlso: NKG2D-CAR constructIn cohorts 1-6, the schedule of administration will be 3 NKR-2 doses administered with a 2-week interval. In absence of progressive disease at the first tumor assessment following NKR-2 administration (on Visit D29 for hematological tumors or on Visit D57 for solid tumors), and according to product availability, the patient will receive a new cycle of 3 administrations maximum with a 2-week interval, at a dose of 1x109 NKR-2 cells per injection, or at the same dose of cycle 1 if it was below 1x109 NKR-2 cells. Patients in cohorts 8-9 (solid arm) and 10-11 (hematological arm) of first segment will receive 3 treatment doses at 1x109 NKR-2 (cohorts 8 and 10) or 3x109 NKR-2 (cohorts 9 and 11) per injection, with a 1-week interval between each dose. A second cycle of three NKR-2 injections at the same dose as in 1st cycle will be administered 2 weeks after the third NKR-2 injection, and with a 2-week interval between each dose. | Biological | Hematological tumors, Solid Tumors |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion
Time frame: 24 months
Safety defined by Occurrence of adverse events (AEs) and serious adverse events (SAEs) during the study treatment until 30 days after the last study treatment administration.
1 secondary outcome
Clinical activity of the treatment in each tumor type
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2019.
- Derived from this study: PubMed 36764323Sallman DA, Kerre T, Havelange V, Poire X, Lewalle P, Wang ES, Brayer JB, Davila ML, Moors I, Machiels JP, Awada A, Alcantar-Orozco EM, Borissova R, Braun N, Dheur MS, Gilham DE, Lonez C, Lehmann FF, Flament A. CYAD-01, an autologous NKG2D-based CAR T-cell therapy, in relapsed or refractory acute myeloid leukaemia and myelodysplastic syndromes or multiple myeloma (THINK): haematological cohorts of the dose escalation segment of a phase 1 trial. Lancet Haematol. 2023 Mar;10(3):e191-e202. doi: 10.1016/S2352-3026(22)00378-7. Epub 2023 Feb 7.
- Derived from this study: PubMed 29133316Lonez C, Verma B, Hendlisz A, Aftimos P, Awada A, Van Den Neste E, Catala G, Machiels JH, Piette F, Brayer JB, Sallman DA, Kerre T, Odunsi K, Davila ML, Gilham DE, Lehmann FF. Study protocol for THINK: a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types. BMJ Open. 2017 Nov 12;7(11):e017075. doi: 10.1136/bmjopen-2017-017075.
- Individual participant dataSharing planned: No
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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.
Amélie Vanneste contact
Anne Flament, MD contact
Frédéric Lehmann, MD principal investigator
Celyad Oncology SA
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NKR-2 cells in people with Acute Myeloid Leukemia/Myelodysplastic Syndrome and Multiple Myeloma (MM), run by Celyad Oncology SA at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 19 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium, 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amélie Vanneste (avanneste@celyad.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion (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 NCT03018405, which also lists 2 linked publications.
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 19 Sep 2019.