CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

• ClinicalTrials.gov Identifier: NCT02742727
• Recruitment Status: Unknown
• First Posted: April 19, 2016
• Last Update Posted: December 6, 2016
• Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Collaborators: The First People's Hospital of Hefei; Hefei Binhu Hospital
• Information provided by (Responsible Party): PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Tracking Information

• First Submitted Date: March 31, 2016
• First Posted Date: April 19, 2016
• Last Update Posted Date: December 6, 2016
• Study Start Date: March 2016
• Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2016)

Adverse events attributed to the administration of the anti-CD7 CAR-pNK cells [ Time Frame: 2 years ]

Determine the toxicity profile of the CD7 targeted CAR-pNK cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 13, 2016)

• Clinical response to CD7 CAR-pNK cell infusions [ Time Frame: Safety follow-up is 100 days from last CAR-pNK infusion ]
  Patients with measurable disease will be assessed for the response of their disease to CD7 CAR-pNK cell treatment.
• Determine the existence of CD7-CAR-pNK in vivo [ Time Frame: 1 year ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma
• Official Title: Chimeric Antigen Receptor-Modified pNK Cells for CD7 Positive Relapsed or Refractory Leukemia and Lymphoma
• Brief Summary: The purpose of this study is to evaluate the safety and effectiveness of CAR-pNK cell immunotherapy in patients with CD7 positive relapsed or refractory Leukemia and Lymphoma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myeloid Leukemia
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Prolymphocytic Leukemia
• T-cell Large Granular Lymphocytic Leukemia
• Peripheral T-cell Lymphoma, NOS
• Angioimmunoblastic T-cell Lymphoma
• Extranodal NK/T-cell Lymphoma, Nasal Type
• Enteropathy-type Intestinal T-cell Lymphoma
• Hepatosplenic T-cell Lymphoma

Intervention

Biological: anti-CD7 CAR-pNK cells

The allogeneic NK cells (NK-92 cell line for clinical use) are engineered to contain anti-CD7 attached to TCRzeta, CD28 and 4-1BB signaling domains. These modified cells are called chimeric antigen receptor NK cells with specificity for CD7.

Other Name: chimeric antigen receptor NK cells with specificity for CD7

Study Arms

Experimental: CAR-pNK Cell immunotherapy

Enrolled patients will receive CAR-pNK cell immunotherapy with a novel specific chimeric antigen receptor targeting CD7 antigen by infusion.

Intervention: Biological: anti-CD7 CAR-pNK cells

• Publications *: 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 13, 2016): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2018
• Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Male and female subjects with CD7+ malignancies in patients with no available curative treatment options who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled:

1. Eligible diseases: CD7 positive relapsed or refractory Leukemia and Lymphoma. ￚ Acute myeloid leukemia, previously identified as CD7+ ￚ Precursor T lymphoblast leukemia/lymphoma ￚ T-cell prolymphocytic leukemia ￚ T-cell large granular lymphocytic leukemia ￚ Peripheral T-cell lymphoma, NOS ￚ Angioimmunoblastic T-cell lymphoma ￚ Extranodal NK/T-cell lymphoma, nasal type ￚ Enteropathy-type intestinal T-cell lymphoma ￚ Hepatosplenic T-cell lymphoma
2. Patients 18 years of age or older, and must have a life expectancy > 12 weeks.
3. CD7 is expressed in malignancy tissues by immuno-histochemical (IHC) or Flow cytometry.
4. Assessable disease as measured by laboratory and bone marrow examinations.
5. Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than 60.
6. Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR-pNK cells.
7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
8. Ability to give informed consent.

Exclusion Criteria:

1. Patients with symptomatic central nervous system (CNS) involvement.
2. Pregnant or nursing women may not participate.
3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
4. 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.
5. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
6. Previously treatment with any gene therapy products.
7. The existence of unstable or active ulcers or gastrointestinal bleeding.
8. Patients with a history of organ transplantation or are waiting for organ transplantation.
9. Patients need anticoagulant therapy (such as warfarin or heparin).
10. Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02742727
• Other Study ID Numbers: PG-107-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Original Study Sponsor: Same as current

Collaborators

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

Investigators

• Principal Investigator: Lin Yang, Ph.D.; PersonGen BioTherapeutics (Suzhou) Co., Ltd.

• PRS Account: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Verification Date: December 2016