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

NCT03018405

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Fallopian Tube Carcinoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03018405

Trial Eligibility

Document

Title

  • Brief Title: A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: CYAD-N2T-002
  • NCT ID: NCT03018405

Conditions

  • Acute Myeloid Leukemia/Myelodysplastic Syndrome
  • Multiple Myeloma (MM)

Interventions

DrugSynonymsArms
NKR-2 cellsNKG2D-CAR constructHematological tumors

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Hematological tumorsExperimentalThe 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.
  • NKR-2 cells
Solid TumorsExperimentalThe 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.
  • NKR-2 cells

Eligibility Criteria

        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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion
Time Frame:24 months
Safety Issue:
Description: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

Measure:Clinical activity of the treatment in each tumor type
Time Frame:24 months
Safety Issue:
Description:Clinical activity of the treatment in each tumor type

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celyad Oncology SA

Last Updated

September 19, 2019