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Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-specific Chimeric Antigen Receptor.


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
B-cell Adult Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia

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Trial Information

Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-specific Chimeric Antigen Receptor.


PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of adoptive T cell therapy using ex vivo expanded
autologous CD8+ and CD4+ CD19 chimeric antigen receptor (CAR)-T cells for patients with
advanced CD19+ B cell malignancies.

SECONDARY OBJECTIVES:

I. To determine the duration of in vivo persistence of adoptively transferred T cells, and
the phenotype of persisting T cells.

II. To determine if adoptively transferred T cells traffic to the bone marrow and function
in vivo.

III. To determine if the adoptive transfer of CD19 CAR-T cells results in depletion of CD19+
B cells in vivo as a surrogate for functional activity.

IV. To determine if the adoptive transfer of CD19 CAR-T cells has antitumor activity in
patients with measurable tumor burden prior to T cell transfer.

V. To determine if the adoptive transfer of CD19 CAR-T cells is associated with tumor lysis
syndrome.

OUTLINE: This is a dose-escalation study of autologous CD19 CAR T-cells.

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells intravenously
(IV) over 20-30 minutes on day 0. Treatment may be repeated in 30 days if there is
persistent disease in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up for 15 years.


Inclusion Criteria:



- Patients with:

- Chronic lymphocytic leukemia (CLL) who are beyond first remission and who have
failed combination chemoimmunotherapy with regimens containing a purine analogue
and anti-CD20 antibody or who were not eligible for such therapy; patients with
fludarabine refractory disease are eligible

- Indolent non-Hodgkin lymphoma (NHL) or mantle cell NHL who are beyond first
remission and previously treated with chemoimmunotherapy; patients who have
relapsed following autologous hematopoietic cell transplantation (HCT) are
eligible

- Aggressive NHL such as diffuse large B-cell lymphoma (DLBCL) who have relapsed
or have residual disease following treatment with curative intent; patients must
have relapsed disease following high-dose therapy and autologous HCT or not be
candidates for high-dose therapy due to inability to collect autologous
peripheral blood stem cell (PBSC), advanced age or other co-morbid medical
conditions; patients with CD19 expressing, relapsed acute lymphoblastic leukemia
(ALL) without higher priority treatment options may be considered for inclusion
in this cohort after discussion with the principal investigator (PI)

- Confirmation of diagnosis by internal pathology review of initial or subsequent
biopsy or other pathologic material at the Fred Hutchinson Cancer Research Center
(FHCRC)/Seattle Cancer Care Alliance (SCCA)

- Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or
current tumor specimen

- Karnofsky performance status > 70%

- Negative pregnancy test for women of childbearing potential

- All patients of childbearing potential must be willing to use a physician approved
contraceptive method before, during, and for at least two months after the T cell
infusion

- Ability to understand and provide informed consent

Exclusion Criteria:

- Treatment with other investigational agent(s) within 30 days of enrollment

- Patients requiring corticosteroid therapy at a dose of > 15 mg of prednisone per day
(or equivalent)

- Active autoimmune disease requiring immunosuppressive therapy

- Serum creatinine > 2.5 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) > 5 x upper limit of normal

- Bilirubin > 3.0 mg/dL

- Forced expiratory volume in one second (FEV1) of < 2.0 L

- Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected) < 40%

- Significant cardiovascular abnormalities as defined by any one of the following:
congestive heart failure, clinically significant hypotension, symptomatic coronary
artery disease, or a documented ejection fraction of < 35%

- Patients who are human immunodeficiency virus (HIV) seropositive or who have active
hepatitis B or C

- Men or women of reproductive ability who are unwilling to use effective contraception
or abstinence

- Uncontrolled active infection (bacterial, viral, fungal, mycobacterial) requiring
treatment with intravenous antibiotics, antiviral or antifungal agents, or long-term
treatment with oral agents

- Anticipated survival of < 3 months

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Highest dose of T cells that is estimated to result in grade 3 or greater toxicity, using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, in less than or equal to 1/3 patients and antitumor activity.

Outcome Time Frame:

30 days

Safety Issue:

Yes

Principal Investigator

David Maloney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2639.00

NCT ID:

NCT01865617

Start Date:

May 2013

Completion Date:

Related Keywords:

  • B-cell Adult Acute Lymphoblastic Leukemia
  • B-cell Chronic Lymphocytic Leukemia
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Lymphoproliferative Disorders
  • Waldenstrom Macroglobulinemia
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109