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)

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.


Eligibility Criteria:
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.