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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
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Celyad (formerly named Cardio3 BioSciences)

Tracking Information
First Submitted Date  ICMJE January 10, 2017
First Posted Date  ICMJE January 12, 2017
Last Update Posted Date September 19, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
Safety 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
Clinical activity of the treatment in each tumor type [ Time Frame: 24 months ]
Clinical activity of the treatment in each tumor type
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
Clinical activity of the treatment in each tumor type [ Time Frame: 24 months ]
Clinical anti-tumor effect will be assessed by standard progression- free survival persistence
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications
Official Title  ICMJE 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)
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia/Myelodysplastic Syndrome
  • Multiple Myeloma (MM)
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Biological: NKR-2 cells
  • 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.
    Intervention: Biological: NKR-2 cells
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 18, 2018)
146
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2017)
24
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amélie Vanneste avanneste@celyad.com
Contact: Anne Flament, MD aflament@celyad.com
Listed Location Countries  ICMJE Belgium,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03018405
Other Study ID Numbers  ICMJE CYAD-N2T-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Celyad (formerly named Cardio3 BioSciences)
Study Sponsor  ICMJE Celyad (formerly named Cardio3 BioSciences)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Frédéric Lehmann, MD Celyad (formerly named Cardio3 BioSciences)
PRS Account Celyad (formerly named Cardio3 BioSciences)
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP