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

Multiple Myeloma (MM) Clinical Trial

— THINK  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03018405
• Other study ID #: CYAD-N2T-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2016
• Est. completion date: August 2021

Study information

• Verified date: November 2018
• Source: Celyad (formerly named Cardio3 BioSciences)
• Contact: Amélie Vanneste
• Email: avanneste[@]celyad.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 146
• Est. completion date: August 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia/Myelodysplastic Syndrome
• Multiple Myeloma
• Multiple Myeloma (MM)
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Celyad (formerly named Cardio3 BioSciences)

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical activity of the treatment in each tumor type	Clinical activity of the treatment in each tumor type	24 months