A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications (THINK)
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| ClinicalTrials.gov Identifier: NCT03018405 |
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Recruitment Status : Unknown
Verified November 2018 by Celyad Oncology SA.
Recruitment status was: Recruiting
First Posted : January 12, 2017
Last Update Posted : September 19, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia/Myelodysplastic Syndrome Multiple Myeloma (MM) | Biological: NKR-2 cells | Phase 1 Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 146 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | The maximum number of patients to be enrolled is 146:
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| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Study Start Date : | December 2016 |
| Estimated Primary Completion Date : | May 2021 |
| Estimated Study Completion Date : | August 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Hematological tumors
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.
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Biological: NKR-2 cells
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. Other Name: NKG2D-CAR construct |
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Experimental: Solid Tumors
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.
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Biological: NKR-2 cells
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. Other Name: NKG2D-CAR construct |
- 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.
- Clinical activity of the treatment in each tumor type [ Time Frame: 24 months ]Clinical activity of the treatment in each tumor type
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03018405
| Contact: Amélie Vanneste | avanneste@celyad.com | ||
| Contact: Anne Flament, MD | aflament@celyad.com |
| United States, Florida | |
| Recruiting | |
| Tampa, Florida, United States, 33612 | |
| Contact: Jeff Edelman 813-745-1040 Jeffrey.Edelman@moffitt.org | |
| United States, New York | |
| Recruiting | |
| Buffalo, New York, United States, 14263 | |
| Contact: Amy Whitworth 877-275-7724 ASKRPCI@roswellpark.org | |
| Belgium | |
| Recruiting | |
| Brussels, Belgium, 1200 | |
| Contact: Anne Moxhon +32 2 764.42.17 anne.moxhon@uclouvain.be | |
| Recruiting | |
| Brussels, Belgium | |
| Contact: Michel Dubuisson +32 (0) 2 541 31 79 michel.dubuisson@bordet.be | |
| Recruiting | |
| Ghent, Belgium | |
| Contact: Jonas Segaert 32 (0)9 332 4912 jonas.segaert@uzgent.be | |
| Contact: Liesbeth Delanghe Liesbeth.delanghe@uzgent.be | |
| Principal Investigator: | Frédéric Lehmann, MD | Celyad Oncology SA |
| Responsible Party: | Celyad Oncology SA |
| ClinicalTrials.gov Identifier: | NCT03018405 |
| Other Study ID Numbers: |
CYAD-N2T-002 |
| First Posted: | January 12, 2017 Key Record Dates |
| Last Update Posted: | September 19, 2019 |
| Last Verified: | November 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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Multiple Myeloma Neoplasms, Plasma Cell Myelodysplastic Syndromes Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Bone Marrow Diseases |