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CAR-pNK Cell Immunotherapy for Relapsed/Refractory CD33+ AML

Primary Purpose

Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia With Maturation

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

anti-CD33 CAR-NK cells

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring AML, CD33, CAR-NK

Eligibility Criteria

3 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (>12 weeks to < 2 year survival) with currently available therapies will be enrolled.
CD33+ acute myeloid leukemia CR (complete remission) can not be achieved after at least 2 prior combination chemotherapy regimens.
AML in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.
Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
Residual disease after primary therapy and not eligible for autologous SCT.
All of those patients must also meet the following criteria:

Expected survival > 12 weeks. Creatinine < 2.5 mg/dl ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal Bilirubin < 2.0 mg/dl Any relapse after prior SCT will make patient eligible regardless of other prior therapy.

Adequate venous access for apheresis, and no other contraindications for leukapheresis.

Ability to give informed consent.

Exclusion Criteria:

Pregnant or nursing women may not participate.
Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening.
Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
The existence of unstable or active ulcers or gastrointestinal bleeding.
Patients need anticoagulant therapy (such as warfarin or heparin).
Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).

Sites / Locations

PersonGen BioTherapeutics (Suzhou) Co., Ltd.Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-NK Cell immunotherapy

Arm Description

Enrolled patients will receive CAR-NK cells immunotherapy with a novel specific chimeric antigen receptor targeting CD33 antigen by infusion.

Outcomes

Primary Outcome Measures

Adverse events attributed to the administration of the anti-CD33 CAR-NK cells

Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment

Secondary Outcome Measures

Objective Response Rate

Anti-leukemia responses to anti-CD33 CAR-NK cell infusions

Full Information

NCT ID

NCT02944162

First Posted

October 23, 2016

Last Updated

December 4, 2016

Sponsor

PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Collaborators

The First People's Hospital of Hefei, Hefei Binhu Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02944162

Brief Title

CAR-pNK Cell Immunotherapy for Relapsed/Refractory CD33+ AML

Official Title

Clinical Investigation of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified NK92 Cells in Relapsed and/or Refractory Acute Myeloid Leukemias

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Unknown status

Study Start Date

October 2016 (undefined)

Primary Completion Date

September 2017 (Anticipated)

Study Completion Date

September 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Collaborators

The First People's Hospital of Hefei, Hefei Binhu Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this clinical trial is to study genetically engineered NK92 cell therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.

Detailed Description

PRIMARY OBJECTIVES: Determine the safety and feasibility of the chimeric antigen receptor NK92 cells transduced with the anti-CD33 vector (referred to as anti-CD33 CAR-NK cells). SECONDARY OBJECTIVES: I. For patients with detectable disease, measure anti-leukemia response due to anti-CD33 CAR-NK cell infusions. II. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by anti-CD33 CAR-NK in vitro. III. Determine if cellular or humoral host immunity develops against the murine anti-CD33. OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD33 CAR-NK (coupled with CD28, CD137 and CD3 zeta signalling domains) vector-transduced NK92 cell line on days 0,3, and 5 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 10 years.

6. Conditions and Keywords

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

Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia With Maturation, Acute Myeloid Leukemia Without Maturation, ANLL

Keywords

AML, CD33, CAR-NK

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR-NK Cell immunotherapy

Arm Type

Experimental

Arm Description

Enrolled patients will receive CAR-NK cells immunotherapy with a novel specific chimeric antigen receptor targeting CD33 antigen by infusion.

Intervention Type

Biological

Intervention Name(s)

anti-CD33 CAR-NK cells

Other Intervention Name(s)

Chimeric antigen receptor NK92 cells with specificity for CD33

Intervention Description

The allogeneic NK cells (NK-92 cell line for clinical use) are engineered to contain anti-CD33 attached to TCRzeta, CD28 and 4-1BB signaling domains. These modified cells are called chimeric antigen receptor NK cells with specificity for CD33.

Primary Outcome Measure Information:

Title

Adverse events attributed to the administration of the anti-CD33 CAR-NK cells

Description

Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment

Time Frame

One year

Secondary Outcome Measure Information:

Title

Objective Response Rate

Description

Anti-leukemia responses to anti-CD33 CAR-NK cell infusions

Time Frame

Up to one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (>12 weeks to < 2 year survival) with currently available therapies will be enrolled. CD33+ acute myeloid leukemia CR (complete remission) can not be achieved after at least 2 prior combination chemotherapy regimens. AML in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor. Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year). Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT. Residual disease after primary therapy and not eligible for autologous SCT. All of those patients must also meet the following criteria: Expected survival > 12 weeks. Creatinine < 2.5 mg/dl ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal Bilirubin < 2.0 mg/dl Any relapse after prior SCT will make patient eligible regardless of other prior therapy. Adequate venous access for apheresis, and no other contraindications for leukapheresis. Ability to give informed consent. Exclusion Criteria: Pregnant or nursing women may not participate. Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening. Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders. History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. The existence of unstable or active ulcers or gastrointestinal bleeding. Patients need anticoagulant therapy (such as warfarin or heparin). Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).

Central Contact Person:

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

Lin Yang, Ph.D

Phone

86-512-65922190

info@persongen.com

Facility Information:

Facility Name

PersonGen BioTherapeutics (Suzhou) Co., Ltd.

City

Suzhou

State/Province

Jiangsu

ZIP/Postal Code

215123

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lin Yang, Ph.D

Phone

86-512-65922190

info@persongen.com

First Name & Middle Initial & Last Name & Degree

Yangyi Bao, MD

First Name & Middle Initial & Last Name & Degree

Xiang Sun, MD

First Name & Middle Initial & Last Name & Degree

Lin Yang, Ph.D

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

(1) The use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (2) Seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (3) Establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD.

Citations:

PubMed Identifier

28054442

Citation

Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.

Results Reference

derived

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CAR-pNK Cell Immunotherapy for Relapsed/Refractory CD33+ AML

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