Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas
Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas With no Available Potentially - Curative Treatment Options Who Have a Limited Prognosis With Currently Available Therapies.
Conditions: official terms
Lymphoma - Lymphoma, B-Cell - Lymphoma, Non-Hodgkin
Study Type
Study Phase
Phase 2
Study Design
Primary Purpose: Treatment
Name: CART-19
Type: Biological
Overall Status
This is a single cohort, open-label pilot study to estimate the efficacy of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as CART-19 or CTL019 cells) in non-Hodgkins Lymphoma (NHL) patients. Single infusion of CART-19 cells administered by i.v.

Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Male or female subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic SCT) who have a limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled. The study will enroll 30 patients, but will ensure that at least 8 patients each with DLBCL, MCL and FL are included.

1. CD19+ lymphoma

a. Follicular lymphoma, previously identified as CD19+ i. At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) ii. Patients who progress within 2 years after second or higher line of therapy will be eligible. For instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible. Patients may have progression, stable disease or responding disease at the time of enrollment.

iii. Patients with a history of large cell transformation are eligible. b. Mantle cell lymphoma i. Beyond 1st CR with relapsed disease, progressive disease during first line rituximab-chemotherapy combination, or persistent disease after first line rituximab-chemotherapy combination and not eligible or appropriate for conventional allogeneic or autologous SCT.

ii. Relapsed after prior autologous SCT. c. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.

2. Age ≥18 years

3. Expected survival > 12 weeks

4. Creatinine < 1.6 mg/dL

5. ALT/AST < 3x upper limit of normal

6. Bilirubin <2.0 mg/dL, unless subject has Gilbert's Syndrome (<3.0 mg/dL)

7. Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy.

8. Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and

1. Have experienced graft rejection (no evidence of donor cells by STR analysis on 2 occasions separated by at least 1 month).

2. Have no active GVHD and require no immunosuppression

3. Are more than 6 months from transplant

9. Measurable or assessable disease according to the "Revised Response Criteria for Malignant Lymphoma" (Cheson et al., J. Clin. Onc., 1999)105. Patients in complete remission with no evidence of disease are not eligible.

10. Performance status (ECOG) 0 or 1.

11. Written informed consent is given.

12. Successful T cell test expansion (first 10 subjects

Exclusion Criteria:

- 1. Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before infusion.

2. Uncontrolled active infection. 3. Active hepatitis B or hepatitis C infection. 4. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.

5. Any uncontrolled active medical disorder that would preclude participation as outlined.

6. HIV infection. 7. Patients with active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment 8. Patients in complete remission with no assessable disease.
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Status: Recruiting
Contact: Stephen Schuster, MD - 855-216-0098 -
Start Date
January 2014
Completion Date
July 2015
Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Record processing date processed this data on July 28, 2015 page