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Dose Optimization Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART-19) in Patients With Relapsed or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL

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Trial Information

Dose Optimization Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART-19) in Patients With Relapsed or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)


This study is being conducted to determine the optimal dose of autologous CART-19 T cells
engineered to express anti-CD19 chimeric antigen receptors in patients with relapsed or
refractory CD19 positive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
(SLL). The two dose levels being assessed are 1-5x10e8 versus 1-5x10e7. The trial will be
conducted in two stages. In stage I subjects will be randomized into one of the two dose
cohort with a1:1 ratio for a total of 12 subjects per dose cohort. Stage II will be to
enroll an additional 8 subjects to the selected dose cohort once safety, tolerability and
clinical responses have been evaluated to determine the optimal dose cohort.


Inclusion Criteria:



- Documented CD19+ CLL or SLL

- Successful test expansion of T-cells (as described in Section 6.1)

- At least 2 prior chemotherapy regimens. At least one fludarabine or other nucleoside
analog containing regimen. Chemotherapy in combination with monoclonal antibody
(Rituxan) will be considered one prior regimen, but single agent Rituxan will not be
considered one prior regimen. Single agent ofatumumbab will be counted as a regimen.

- Less than 2 years between last therapy and progression (e.g. most recent progression
free interval 2 years)

- Subject has no available or declines curative treatment options such as allogeneic
SCT and has limited prognosis (2 years survival) with currently available therapies

- Expected survival 12 weeks

- Performance status (ECOG) 0 or 1

- Age greater than or equal to 18 years

- Adequate organ system function including:

1. Creatinine 1.6 mg/dl

2. ALT/AST 3x upper limit of normal

3. Direct Bilirubin 2.0 mg/dl

- Any relapse after prior autologous SCT will make patient eligible regardless of other
prior therapy

- Patients with relapsed disease after prior allogeneic SCT (myeloablative or
nonmyeloablative) will be eligible if they meet all other inclusion criteria and:

1. experienced graft rejection (no evidence of donor cells by STR analysis on 2
occasions separated by at least 1 month)

2. Have no active GVHD and require no immunosuppression

3. Are more than 6 months from transplant

- No contraindications for leukapheresis

- Gives voluntary informed consent

Exclusion Criteria:

- 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. 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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Adverse Events

Outcome Time Frame:

12 months

Safety Issue:

Yes

Principal Investigator

Noelle Frey, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania

Authority:

United States: Food and Drug Administration

Study ID:

UPCC 03712

NCT ID:

NCT01747486

Start Date:

December 2012

Completion Date:

December 2015

Related Keywords:

  • Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL
  • Leukemia, Lymphocytic, Chronic, B-Cell

Name

Location

Abramsonc Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104