Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01865617
First received: May 28, 2013
Last updated: May 18, 2015
Last verified: May 2015
  Purpose

This phase I/II trial studies the side effects and best dose of laboratory treated T cells to see how well they work in treating patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia that have come back or does not respond to treatment. T cells that are treated in the laboratory before being given back to the patient may make the body build an immune response to kill cancer cells.


Condition Intervention Phase
Chronic Lymphocytic Leukemia in Remission
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Chronic Lymphocytic Leukemia
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Non-Hodgkin Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Diffuse Large B-Cell Lymphoma
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Other: Laboratory Biomarker Analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia/Lymphoma and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Death within 8 weeks of the study cell infusion thought to be definitely or probably related to CAR T cell therapy. [ Time Frame: Within 8 weeks of the study cell infusion ] [ Designated as safety issue: Yes ]
  • Duration of persistence of adoptively transferred CD19 CAR-T cells [ Time Frame: Up to day 365 ] [ Designated as safety issue: No ]
    Descriptive statistics will be used and 95% confidence intervals will be calculated when appropriate.

  • Highest dose of T cells that is estimated to result in grade 3 or greater toxicity, using Common Terminology Criteria for Adverse Events version 4.0, in less than or equal to 1/3 patients [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Migration of adoptively transferred CD19 CAR-T cells [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Descriptive statistics will be used and 95% confidence intervals will be calculated when appropriate.

  • Objective response rate of complete remission and partial remission [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Descriptive statistics will be used and 95% confidence intervals will be calculated when appropriate.

  • Overall survival [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be used and 95% confidence intervals will be calculated when appropriate.

  • Progression free survival [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be used and 95% confidence intervals will be calculated when appropriate.


Estimated Enrollment: 125
Study Start Date: May 2013
Estimated Primary Completion Date: April 2029 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (anti-CD19-CAR autologous T cells)
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in 21 days if there is persistence disease in the absence of unacceptable toxicity.
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of adoptive T cell therapy using ex vivo expanded autologous cluster of differentiation (CD) 8+ 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 21 days if there is persistent disease in the absence of unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

INCLUSIONS FOR SCREENING AND LEUKAPHERESIS

  • Patients with CD19 expressing acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL)
  • Ability to understand and provide informed consent
  • Not human immunodeficiency virus (HIV) infected

INCLUSIONS FOR CAR-T CELL THERAPY

  • Patients with:

    • 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; patients may be treated following allogeneic hematopoietic cell transplant (HCT)
    • Indolent NHL or mantle cell NHL who are beyond first remission and previously treated with chemoimmunotherapy or who were not eligible for such therapy; patients who have relapsed following autologous or allogeneic 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 should have relapsed following, or not be eligible for high-dose therapy and autologous HCT; patients with chemotherapy refractory disease or marrow involvement or comorbidities precluding successful autologous HCT are eligible; patients may be treated following allogeneic HCT
    • Patients with CD19 expressing, relapsed ALL
  • Confirmation of diagnosis
  • Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology
  • Karnofsky performance status >= 60%
  • 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:

EXCLUSIONS FOR CAR-T CELL THERAPY

  • Patients requiring corticosteroid therapy at a dose of > 15 mg of prednisone per day (or equivalent)
  • Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the Principal Investigator (PI)
  • 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% will be excluded
  • Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < 35%
  • Uncontrolled active infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01865617

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: David G. Maloney    206-667-5616      
Principal Investigator: David G. Maloney         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01865617     History of Changes
Other Study ID Numbers: 2639.00, NCI-2013-00073, 2639, 2639.00, P30CA015704, R01CA136551
Study First Received: May 28, 2013
Last Updated: May 18, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 01, 2015