NCT03018405

Brief 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 cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma).

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
146

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2016

Longer than P75 for phase_1

Geographic Reach
2 countries

5 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2016

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 10, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 12, 2017

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2021

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2021

Completed
Last Updated

September 19, 2019

Status Verified

November 1, 2018

Enrollment Period

4.4 years

First QC Date

January 10, 2017

Last Update Submit

September 18, 2019

Conditions

Acute Myeloid Leukemia/Myelodysplastic SyndromeMultiple Myeloma (MM)

Outcome Measures

Primary Outcomes (1)

  • 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.

    24 months

Secondary Outcomes (1)

  • Clinical activity of the treatment in each tumor type

    24 months

Study Arms (2)

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.

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.

Biological: NKR-2 cells

Interventions

NKR-2 cellsBIOLOGICAL

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.

Also known as: NKG2D-CAR construct
Hematological tumorsSolid Tumors

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Unknown Facility

Tampa, Florida, 33612, United States

RECRUITING

Unknown Facility

Buffalo, New York, 14263, United States

RECRUITING

Unknown Facility

Brussels, 1200, Belgium

RECRUITING

Unknown Facility

Brussels, Belgium

RECRUITING

Unknown Facility

Ghent, Belgium

RECRUITING

Related Publications (2)

  • 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.

    PMID: 36764323DERIVED

  • Lonez 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.

    PMID: 29133316DERIVED

MeSH Terms

Conditions

GATA2 DeficiencyMultiple Myeloma

Condition Hierarchy (Ancestors)

Myelodysplastic SyndromesBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Frédéric Lehmann, MD

    Celyad Oncology SA

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Amélie Vanneste

CONTACT

avanneste@celyad.com

Anne Flament, MD

CONTACT

aflament@celyad.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: 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).
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2017

First Posted

January 12, 2017

Study Start

December 1, 2016

Primary Completion

May 1, 2021

Study Completion

August 1, 2021

Last Updated

September 19, 2019

Record last verified: 2018-11

Data Sharing

IPD Sharing
Will not share

Locations

US(2)BE(3)