Pilot Trial Of Autologous T Cells Engineered To Express Anti-CD19 Chimeric Antigen Receptor (CART19)In Combination With Ibrutinib In Patients With Relapsed Or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)Or Small Lymphocytic Lymphoma (SLL)

Pilot Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART19) in Combination With Ibrutinib in Patients With Relapsed or Refractory CD19+ CLL or SLL

Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. 15 evaluable subjects (adults) with relapsed or refractory CLL/SLL who have achieved partial response or stable disease on ibrutinib therapy will be eligible to receive CART-19 therapy.

Inclusion Criteria:

• Documented CD19+ CLL or SLL

• Successful test expansion -cells (as described in Section 6.1)

• Patients must have failed at least 1 prior regimen before Ibrutinib (not including single agent rituximab or single agent corticosteroids)

  a. Note: Any relapse after prior autologous SCT will make the patient eligible regardless of other prior therapy.

• Patients must be currently receiving ibrutinib for at least 6 months prior to enrollment in the study and:

  1. Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity
  2. The best response to ibrutinib therapy must not have exceeded partial response or stable disease (i.e. no CR or CRi)
  3. Note: Patients carrying a deletion at chromosome 17p (i.e. del[17p]), and/or TP53, BTK, and at the PLCγ2 loci mutations, will be eligible if they are receiving frontline therapy with ibrutinib.

• ECOG Performance status 0 or 1

• 18 years of age and older

• Adequate organ system function including:

  1. Creatinine < 1.6 mg/dl
  2. ALT/AST < 3x upper limit of normal
  3. Total Bilirubin <2.0 mg/dl with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.

• Patients with relapsed disease after prior allogeneic SCT (myeloablative or nonmyeloablative) will be eligible if they meet all other inclusion criteria and:

  1. Have no active GVHD and require no immunosuppression
  2. Are more than 6 months from transplant

• No contraindications for leukapheresis

• Left Ventricular Ejection fraction >40%

• Gives voluntary informed consent

• Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria:

• CLL patients with known or suspected transformed disease (i.e. Richter's transformation). Note: biopsy proven absence of transformation is not required.
• 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 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 or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary.
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• HIV infection.
• Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.