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Clinical Study of Chimeric CD(Cluster of Differentiation)19 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas


N/A
5 Years
90 Years
Open (Enrolling)
Both
Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Refractory Chronic Lymphocytic Leukemia, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma

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Trial Information

Clinical Study of Chimeric CD(Cluster of Differentiation)19 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas


PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced
with the anti-CD19 (cluster of differentiation antigen 19 ) vector (referred to as CART-19
cells).

II. Determine duration of in vivo survival of CART-19 cells. RT-PCR (reverse transcription
polymerase chain reaction) analysis of whole blood will be used to detect and quantify
survival of CART-19 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to CART-19 cell
infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as
measured by the relative engraftment levels of CART-19 TCR zeta:CD137 and TCR zeta cells
over time.

III. Estimate relative trafficking of CART-19 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells (such as patients with active chronic
lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell
killing by CART-19 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and
assess correlation with loss of detectable CART-19 (loss of engraftment).

VI. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 group according to order of enrollment.

Patients receive anti-CD19-CAR (coupled with CD137 and CD3 zeta signalling
domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3
months for 2 years, and annually thereafter for 13 years.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Occurrence of study related adverse events

Outcome Description:

defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment

Outcome Time Frame:

Until week 24

Safety Issue:

Yes

Authority:

China: Ethics Committee

Study ID:

CHN-PLAGH-BT-005

NCT ID:

NCT01864889

Start Date:

April 2013

Completion Date:

April 2017

Related Keywords:

  • Hematopoietic/Lymphoid Cancer
  • Adult Acute Lymphoblastic Leukemia in Remission
  • B-cell Adult Acute Lymphoblastic Leukemia
  • B-cell Chronic Lymphocytic Leukemia
  • Prolymphocytic Leukemia
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage III Chronic Lymphocytic Leukemia
  • Stage III Grade 1 Follicular Lymphoma
  • Stage III Grade 2 Follicular Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Chronic Lymphocytic Leukemia
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Prolymphocytic
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Mantle-Cell

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