Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by CART19 (CART19)

This is an interventional treatment trial for Hematopoietic/Lymphoid Cancer Read More

Inclusion Criteria:

• 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(second complete remission) or CR3(third complete remission) 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(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible.
  • Mantle cell lymphoma:
  • Beyond 1st CR (complete remission) 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(alanine aminotransferase)/AST (aspartate aminotransferase)< 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 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
  • 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/CD137 costimulation
  • Any uncontrolled active medical disorder that would preclude participation as outlined
  • HIV infection