Description:
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.
Title
- Brief Title: 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)
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
UPCC 18415, 823584
- NCT ID:
NCT02640209
Conditions
- LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)
Interventions
Drug | Synonyms | Arms |
---|
CART 19 | | Arm 1 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm 1 | Experimental | | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Adverse Events |
Time Frame: | 26 months |
Safety Issue: | |
Description: | |
Details
Phase: | Early Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | University of Pennsylvania |
Last Updated
May 7, 2020