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)



Status:Active, not recruiting
Conditions:Blood Cancer, Lymphoma
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:11/9/2018
Start Date:December 2015
End Date:October 2019

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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

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.
We found this trial at
1
site
3400 Civic Center Blvd
Philadelphia, Pennsylvania 19104
(215) 662-6065
Phone: 855-216-0098
Abramson Cancer Center of the University of Pennsylvania The Abramson Cancer Center of the University...
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mi
from
Philadelphia, PA
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