Know Cancer

or
forgot password

Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma


N/A
18 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

Thank you

Trial Information

Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma


PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced
with the anti-CD20 vector (referred to as CART-20 cells).

II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood
will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB and TCR zeta cells
over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to CART-20 cell
infusions.

II. To determine if the 4-1BB transgene is superior to the TCR zeta only transgene as
measured by the relative engraftment levels of CART-20 TCR zeta:4-1BB and TCR zeta cells
over time.

III. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells (such as patients with active CLL,
ALL, etc) determine tumor cell killing by CART-20 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and
assess correlation with loss of detectable CART-20 (loss of engraftment).

VI. Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 of 2 groups according to order of enrollment.

Group 1 (Patients 1-5): Patients receive anti-CD20-CAR vector-transduced autologous T cells
with 41BB-gamma vector on days 0,1, 2, and 11 in the absence of disease progression or
unacceptable toxicity.

Group 2 (Patients 6-10): Patients receive anti-CD20-CAR vector-transduced autologous T cells
with either 41BB-gamma vector or TCR zeta vector on days 0,1, 2, and 11 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 CD20+ 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

- CD20+ 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 CD20+:

- 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 CD20+:

- 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 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/CD28
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 of Chinese PLA General Hospital

Study ID:

CHN-PLAGH-BT-001

NCT ID:

NCT01735604

Start Date:

January 2013

Completion Date:

October 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

Name

Location