CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy
Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia
About this trial
This is an interventional treatment trial for Hematopoietic/Lymphoid Cancer
Eligibility Criteria
Inclusion
- Male and female subjects with CD19+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled
- CD19+ leukemia or lymphoma
- ALL in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor
- Follicular lymphoma, previously identified as CD19+:
- At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy
- Stage III-IV disease
- Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year)
- Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)
- CLL:
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior
- Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval < 2 years)
- Not eligible or appropriate for conventional allogeneic SCT
- Patients who achieve only a partial response to FCR as initial therapy will be eligible.
- Mantle cell lymphoma:
- Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT
- Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...)
- Relapsed after prior autologous SCT
- B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT
- Diffuse large cell lymphoma, previously identified as CD19+:
- Residual disease after primary therapy and not eligible for autologous SCT
- Relapsed after prior autologous SCT
- Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous SCT
- Expected survival > 12 weeks
- Creatinine < 2.5 mg/dl
- ALT/AST < 3x normal
- Bilirubin < 2.0 mg/dl
- Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
- Adequate venous access for apheresis, and no other contraindications for leukapheresis
- Voluntary informed consent is given
Exclusion
- 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
- Previously treatment with any gene therapy products
- Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD28 costimulation
- Any uncontrolled active medical disorder that would preclude participation as outlined
- HIV infection
Sites / Locations
- Abramson Cancer Center of The University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
CART-19 CLL
CART-19 ALL
CART-19 (autologous T cells transduced with CD19 TCR-ζ/4-1BB vector) administered as an IV infusion days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity.Minimum/maximum total dose: 1.5x10^7 / 5x10^9 administered to patients with chronic Lymphocytic Leukemia (CLL) and Acute Lymphoblastic Leukemia (ALL).
CART-19 (autologous T cells transduced with CD19 TCR-ζ/4-1BB vector) administered as an IV infusion days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity.Minimum/maximum total dose: 1.5x10^7 / 5x10^9 administered to patients with chronic Lymphocytic Leukemia (CLL) and Acute Lymphoblastic Leukemia (ALL).