LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)
Conditions
Brief 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.
Interventions
BIOLOGICALCART 19
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).
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Adverse Events | 26 months |
Countries
United States
Outcome results
None listed