CAR T Cells Targeting CD30 Positive Lymphomas (4SCAR30273)

Lymphomas Clinical Trial

Official title:

Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Relapsed and Refractory CD30 Positive Lymphomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02274584
• Other study ID #: 30273-4SCAR
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: October 22, 2014
• Last updated: October 22, 2014
• Start date: March 2014
• Est. completion date: October 2017

Study information

• Verified date: October 2014
• Source: Peking University
• Contact: Jun Zhu, MD
• Phone: +861088196596
• Email: zj[@]bjcancer.org
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Currently, a majority of lymphomas cannot be cured by standard chemo-radiotherapy. Cluster of differentiation antigen 30 (CD30) is expressed in many lymphoma subtypes, such as Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). CD30 represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This study will evaluate a novel 4th generation CD30 CAR engineered with a self-withdrawal mechanism (FKBP-iCasp9) for both efficacy and safety evaluation in lymphoma patients.

Description:

A large number of lymphoma patients exhaust current treatment options and die from the disease. Innovative therapy is urgently needed. Chimeric antigen receptor (CAR)-modified T cells have demonstrated unprecedented successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. Besides CD19 lymphomas, many lymphomas are CD30 positive and therefore, CD30-CAR T cells may prove to be effective in treating such patients. We have developed several generations of CD30 CARs. Preclinical studies have demonstrated effective killing of CD30 target cells. In this study, two versions of CD30 CARs, both of which are 4th generation CARs with a self-withdrawal mechanism (FKBP-iCasp9), will be evaluated in CD30 lymphoma patients. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Relapsed or refractory CD30(+) lymphoma patients proved by immuno-histochemistry (IHC) or Flow-cytometry.

• Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

• Age=18.

• Pulse oximetry of > 90% on room air.

• Adequate hepatic function, defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN), aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.

• Adequate renal function, defined as serum creatinine <2.0mg/dl.

• Adequate heart function with LVEF=50%

• Hb=80g/L

• Measurable disease can be identified.

• Life expectancy =3 months.

• Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 1 year after the study is concluded. The male partner should use a condom.

• Patients must sign an informed consent.

Exclusion Criteria:

• Uncontrolled active infection.

• Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).

• HIV positive

• Pregnant or lactating.

• Currently enrolled in another clinical trial.

• Concurrent use of systemic steroids.

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphomas

Intervention

Genetic:
• Anti-CD30 CAR T cells
Autologous 4th generation withdrawal lentiviral-transduced anti-CD30 CAR T cells

Locations

Country	Name	City	State
China	Peking University Cancer Hospital	Beijing	Beijing
United States	University of Florida	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Peking University	University of Florida

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events.	Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	2 years.	Yes
Secondary	Survival time of Anti-CD30 CAR T cells in vivo.	Measure the survival of 4th generation CAR T cells transduced with the anti-CD30 lentiviral vector.	2 years.	No
Secondary	Response rates to the 4th generation CAR T cells.	Describe the response rates of patients treated with 4th generation CAR T cells, including partial remission (PR), complete remission (CR), stable disease (SD) and progressive disease (PD).	2 years.	No
Secondary	Survival time of the patients.	Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).	2 years.	No