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

NCT ID: NCT02944162

Last Updated: 2016-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-31

Study Completion Date

2018-09-30

Brief Summary

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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

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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.

Conditions

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

Keywords

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AML CD33 CAR-NK

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CAR-NK Cell immunotherapy

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

Group Type EXPERIMENTAL

anti-CD33 CAR-NK cells

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type BIOLOGICAL

Other Intervention Names

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Chimeric antigen receptor NK92 cells with specificity for CD33

Eligibility Criteria

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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).
Minimum Eligible Age

3 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The First People's Hospital of Hefei

OTHER

Sponsor Role collaborator

Hefei Binhu Hospital

OTHER

Sponsor Role collaborator

PersonGen BioTherapeutics (Suzhou) Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Suzhou, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lin Yang, Ph.D

Role: CONTACT

Phone: 86-512-65922190

Email: [email protected]

Facility Contacts

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Lin Yang, Ph.D

Role: primary

References

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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.

Reference Type DERIVED
PMID: 28054442 (View on PubMed)

Other Identifiers

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PG-0332

Identifier Type: -

Identifier Source: org_study_id