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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02944162
• Other study ID #: PG-0332
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: October 23, 2016
• Last updated: December 4, 2016
• Start date: October 2016
• Est. completion date: September 2018

Study information

• Verified date: October 2016
• Source: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Contact: Lin Yang, Ph.D
• Phone: 86-512-65922190
• Email: info[@]persongen.com
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: September 2018
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 80 Years

Eligibility

Inclusion Criteria:

1. 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.

2. CD33+ acute myeloid leukemia CR (complete remission) can not be achieved after at least 2 prior combination chemotherapy regimens.

3. 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.

4. Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).

5. 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.

6. Residual disease after primary therapy and not eligible for autologous SCT.

7. 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:

1. Pregnant or nursing women may not participate.

2. Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening.

3. 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.

4. History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.

5. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.

6. The existence of unstable or active ulcers or gastrointestinal bleeding.

7. Patients need anticoagulant therapy (such as warfarin or heparin).

8. Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• anti-CD33 CAR-NK cells
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.

Locations

Country	Name	City	State
China	PersonGen BioTherapeutics (Suzhou) Co., Ltd.	Suzhou	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
PersonGen BioTherapeutics (Suzhou) Co., Ltd.	Hefei Binhu Hospital, The First People's Hospital of Hefei

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	One year	Yes
Secondary	Objective Response Rate	Anti-leukemia responses to anti-CD33 CAR-NK cell infusions	Up to one year	Yes