CAR T Cells Targeting CD30 Positive Lymphomas (4SCAR30273)

Sponsor

Peking University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02274584

Collaborator

University of Florida (Other)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphomas	Genetic: Anti-CD30 CAR T cells	Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2014

Anticipated Primary Completion Date :

Oct 1, 2016

Anticipated Study Completion Date :

Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAR T cells Autologous 4th generation anti-CD30 CAR T cells	Genetic: Anti-CD30 CAR T cells Autologous 4th generation withdrawal lentiviral-transduced anti-CD30 CAR T cells

Arm

Intervention/Treatment

Experimental: CAR T cells

Autologous 4th generation anti-CD30 CAR T cells

Genetic: Anti-CD30 CAR T cells

Autologous 4th generation withdrawal lentiviral-transduced anti-CD30 CAR T cells

Outcome Measures

Primary Outcome Measures

Number of patients with adverse events. [2 years.]
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

Survival time of Anti-CD30 CAR T cells in vivo. [2 years.]
Measure the survival of 4th generation CAR T cells transduced with the anti-CD30 lentiviral vector.
Response rates to the 4th generation CAR T cells. [2 years.]
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).
Survival time of the patients. [2 years.]
Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610
2	Peking University Cancer Hospital	Beijing	Beijing	China	100142

Sponsors and Collaborators

Peking University
University of Florida

Investigators

Principal Investigator: Jun Zhu, MD, Peking University Cancer Hospital & Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jun Zhu, Director, Peking University

ClinicalTrials.gov Identifier:

NCT02274584

Other Study ID Numbers:

30273-4SCAR

First Posted:

Oct 24, 2014

Last Update Posted:

Oct 24, 2014

Last Verified:

Oct 1, 2014

Keywords provided by Jun Zhu, Director, Peking University

Hodgkin's lymphoma

Anaplastic large cell lymphoma

CD30 positive lymphoma

Peripheral T/Natural Killer (NK) cell lymphoma

Additional relevant MeSH terms:

Lymphoma

Study Results

No Results Posted as of Oct 24, 2014