Clinical trial NCT02274584: CAR T Cells Targeting CD30 Positive Lymphomas (4SCAR30273)
Official title: Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Relapsed and Refractory CD30 Positive Lymphomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Lymphomas
Keywords: Hodgkin's lymphoma
Anaplastic large cell lymphoma
CD30 positive lymphoma
Peripheral T/Natural Killer (NK) cell lymphoma
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: University of Florida
First posted: 2014-10-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with adverse events.
timeFrame: 2 years.
Secondary outcomes:
measure: Survival time of Anti-CD30 CAR T cells in vivo.
timeFrame: 2 years.
measure: Response rates to the 4th generation CAR T cells.
timeFrame: 2 years.
measure: Survival time of the patients.
timeFrame: 2 years.
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Zhu, MD
role: PRINCIPAL_INVESTIGATOR
References: