CART-19 Cells in Treating Patients With Chemotherapy Relapsed or Refractory B Cell Non-Hodgkin Lymphoma

Status: Closed to Accrual

Description

This phase II clinical trial studies how well CD19CAR-CD3zeta-4-1BB-expressing autologous T-lymphocytes (CART-19 cells) work in treating patients with chemotherapy recurrent or refractory B cell non-Hodgkin lymphoma. This type of non-Hodgkin lymphoma involves a kind of white cell (or lymphocyte) called the B-cell. T-cells are modified through gene transfer using a type of virus called a lentiviral vector to deliver the genetic material called CART-19 into a patient's T-cells. These modified cells are called CART-19 T-cells. The CART-19 T-cells will be able to identify and possibly kill cancerous B-cells and may help the body build an effective immune response to kill cancer cells.

Eligibility Criteria

Inclusion Criteria

  • Subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic stem cell transplant [SCT]) who have a limited prognosis (several months to < 2 year survival) with currently available therapies
  • Follicular lymphoma, previously identified as CD19+ * At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) * 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 * Patients with a history of large cell transformation are eligible
  • Mantle cell lymphoma * 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 * Relapsed after prior autologous SCT
  • Diffuse large B cell lymphoma, previously identified as CD19+ * Residual disease after primary therapy and not eligible for autologous SCT * Relapsed or persistent disease after prior autologous SCT * Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT * Patients with an antecedent history of follicular lymphoma or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are eligible
  • Expected survival > 12 weeks
  • Creatinine < 1.6 mg/dL
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3 x upper limit of normal
  • Bilirubin < 2.0 mg/dL, unless subject has Gilbert’s Syndrome (=< 3.0 mg/dL)
  • Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
  • Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and: * Have experienced graft rejection (no evidence of donor cells by short tandem repeat (STR) analysis on 2 occasions separated by at least 1 month) * Have no active graft-vs-host disease (GVHD) and require no immunosuppression * Are more than 6 months from transplant
  • 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
  • Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 or 1
  • Written informed consent is given
  • Successful T cell test expansion (first 10 subjects)

Exclusion Criteria

  • Pregnant or lactating women; female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
  • Uncontrolled active infection
  • Active hepatitis B or hepatitis C infection
  • Concurrent use of systemic steroids; recent or current use of inhaled steroids is not exclusionary
  • Any uncontrolled active medical disorder that would preclude participation as outlined
  • Human immunodeficiency virus (HIV) infection
  • Patients with active central nervous system (CNS) involvement by malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment
  • Patients in complete remission with no assessable disease

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To estimate the efficacy of a single target dose of 1-5 x10^8 CART-19 cells for patients with advanced B cell non-Hodgkin’s lymphoma (NHL); describe overall response rate for patients with NHL.

SECONDARY OBJECTIVES:

I. Determine persistence, trafficking and function of CART-19 cells.

II. Determine the effects of CART-19 infusion on B cells and CD19 expression in vivo.

III. Evaluate impact of CART-19 treatment on systemic soluble immune factors in patients.

IV. Determine if cellular or humoral host immunity develops against CART-19 cells.

V. Characterize the relative subsets of CART-19 T cells (central memory T cells [Tcm], effector memory T cells [Tem], and regulatory T cells [Treg]).

VI. Evaluate minimal residual disease (MRD) using molecular technologies.

VII. Describe overall response rate (ORR) for each individual histology (minimum n = 8), complete remission (CR), complete remission unconfirmed (CRu) and partial remission (PR) rate.

VIII. Describe overall survival (OS) and progression-free survival (PFS) for all patients.

IX. Describe duration of response (DOR) for responding patients.

X. Assess the safety and tolerability of CART-19 in NHL subjects by recording the frequency and severity of adverse events reporting, including but not limited to, estimating the frequency of cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).

XI. Determine the dose manufacturing feasibility.

XII. Follow subjects infused with less than protocol-specified target dose.

OUTLINE:

Patients receive CART-19 cells intravenously (IV) on day 0.

After completion of study treatment, patients are followed up periodically for up to 15 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pennsylvania / Abramson Cancer Center

Principal Investigator
Stephen John Schuster

Trial IDs

Primary ID UPCC13413
Secondary IDs NCI-2014-00173, 818607, UPCC 13413
Clinicaltrials.gov ID NCT02030834