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)

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Biological: CART 19


Participation Criteria
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Eligibility Criteria
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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: Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity The best response to ibrutinib therapy must not have exceeded partial response or stable disease (i.e. no CR or CRi) 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: Creatinine < 1.6 mg/dl ALT/AST < 3x upper limit of normal 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: Have no active GVHD and require no immunosuppression 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Biological: CART 19<br>* The target dose range administered in this study is 1-5x108 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x107 CART19), 30% on Day 1 (3x107-1.5x108 CART19), 60% on Day 2 (6x107-3x108 CART19).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events |  | 26 months |