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)

Conditions: LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Summary: 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.