ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03018405
Previous Study | Return to List | Next Study

A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications (THINK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03018405
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Celyad (formerly named Cardio3 BioSciences)

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).

Condition or disease Intervention/treatment Phase
Colorectal Cancer (CRC) Ovarian Cancer (Epithelial and Fallopian Tube ) Urothelial Carcinoma Triple-negative Breast Cancer (TNBC) Pancreatic Cancer Acute Myeloid Leukemia/Myelodysplastic Syndrome Multiple Myeloma (MM) Biological: NKR-2 cells Phase 1 Phase 2

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 : 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:

  • 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
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
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.
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

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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Clinical activity of the treatment in each tumor type [ Time Frame: 24 months ]
    Clinical activity of the treatment in each tumor type



Information from the National Library of Medicine

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
Criteria

Inclusion Criteria:

  1. Men or women ≥ 18 years old at the time of signing the ICF
  2. Pati• 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.

Detailed disease specific criteria exist and can be discussed with contacts listed below.

Exclusion Criteria:

1. 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).

Information from the National Library of Medicine

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


Contacts
Contact: Jim Kostka Think_info@celyad.com
Contact: Anne Flament, MD aflament@celyad.com

Locations
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   
Sponsors and Collaborators
Celyad (formerly named Cardio3 BioSciences)
Investigators
Principal Investigator: Frédéric Lehmann, MD Celyad (formerly named Cardio3 BioSciences)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celyad (formerly named Cardio3 BioSciences)
ClinicalTrials.gov Identifier: NCT03018405     History of Changes
Other Study ID Numbers: CYAD-N2T-002
First Posted: January 12, 2017    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Colorectal Neoplasms
Multiple Myeloma
Pancreatic Neoplasms
Myelodysplastic Syndromes
Preleukemia
Triple Negative Breast Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Plasma Cell
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders