Back to results

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

Primary Purpose

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

Status

Unknown status

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

NKR-2 cells

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia/Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Recruiting
Recruiting
Recruiting
Recruiting
Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Hematological tumors

Solid Tumors

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Clinical activity of the treatment in each tumor type

Full Information

NCT ID

NCT03018405

First Posted

January 10, 2017

Last Updated

September 18, 2019

Sponsor

Celyad Oncology SA

1. Study Identification

Unique Protocol Identification Number

NCT03018405

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Unknown status

Study Start Date

December 2016 (undefined)

Primary Completion Date

May 2021 (Anticipated)

Study Completion Date

August 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celyad Oncology SA

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

Non-Randomized

Enrollment

146 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hematological tumors

Arm Type

Experimental

Arm Description

Arm Title

Solid Tumors

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

NKR-2 cells

Other Intervention Name(s)

NKG2D-CAR construct

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion

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.

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Clinical activity of the treatment in each tumor type

Description

Clinical activity of the treatment in each tumor type

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amélie Vanneste

avanneste@celyad.com

First Name & Middle Initial & Last Name or Official Title & Degree

Anne Flament, MD

aflament@celyad.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frédéric Lehmann, MD

Organizational Affiliation

Celyad Oncology SA

Official's Role

Principal Investigator

Facility Information:

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jeff Edelman

Phone

813-745-1040

Jeffrey.Edelman@moffitt.org

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amy Whitworth

Phone

877-275-7724

ASKRPCI@roswellpark.org

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anne Moxhon

Phone

+32 2 764.42.17

anne.moxhon@uclouvain.be

City

Brussels

Country

Belgium

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michel Dubuisson

Phone

+32 (0) 2 541 31 79

michel.dubuisson@bordet.be

City

Ghent

Country

Belgium

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jonas Segaert

Phone

32 (0)9 332 4912

jonas.segaert@uzgent.be

First Name & Middle Initial & Last Name & Degree

Liesbeth Delanghe

Liesbeth.delanghe@uzgent.be

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29133316

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs