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

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01865617
Collaborator
National Cancer Institute (NCI) (NIH)
204
Enrollment
1
Location
13
Arms
94.1
Actual Duration (Months)
2.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 have not responded 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.

Detailed Description

PRIMARY OBJECTIVES:
  1. To evaluate the feasibility and safety of adoptive T cell therapy using ex vivo expanded autologous CD8 positive (+) and CD4+ CD19 chimeric antigen receptor (CAR)-T cells for patients with advanced CD19+ B cell malignancies.
SECONDARY OBJECTIVES:
  1. To determine the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.

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

  3. 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.

  4. 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.

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

OUTLINE: This is a phase I, dose-escalation study of autologous CD19 CAR T-cells followed by a phase II study.

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 no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity.

DOSE DENSE EXPANSION COHORT: An additional cohort will receive a second anti-CD19-CAR lentiviral vector-transduced autologous T cell infusion without additional lymphodepleting chemotherapy 10-21 days after the first infusion if adequate CD19 CAR-T cells can be produced and appropriate criteria are met.

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

Study Design

Study Type:
Interventional
Actual Enrollment :
204 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (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
Actual Study Start Date :
May 22, 2013
Actual Primary Completion Date :
Mar 26, 2021
Actual Study Completion Date :
Mar 26, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: ALL (high tumor burden) dose level 1

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 1 up to 2x105 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: ALL (high tumor burden) dose level 2

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 2 up to 2x106 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: ALL (high tumor burden) dose level 3

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 3 up to 2x107 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: ALL (low tumor burden) dose level 1

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: low Dose level: 1 up to 2x105 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: ALL (low tumor burden) dose level 2

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 2 up to 2x106 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: CLL dose level 1

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL Dose level: 1 up to 2x105 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: CLL dose level 2

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL Dose level: 2 up to 2x106 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: CLL dose level 3

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL Dose level: 3 up to 2x107 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: CLL (ibrutinib) dose level 2

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL (ibrutinib) Dose level: 2 up to 2x106 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: NHL dose level 1

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 1 up to 2x105 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: NHL dose level 2

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 2 up to 2x106 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: NHL dose level 3

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 3 up to 2x107 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: NHL (dose dense) dose level 2

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 2 up to 2x106 EGFR+ cells/kg

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Outcome Measures

Primary Outcome Measures

  1. Death within 8 weeks of the study cell infusion thought to be definitely or probably related to chimeric antigen receptor (CAR) T cell therapy [Within 8 weeks of the study cell infusion]

    Death within 8 weeks of the study cell infusion thought to be definitely or probably related to CAR T cell therapy will be assessed.

  2. 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 [30 days]

    The 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 will be evaluated.

  3. Objective response rate of complete remission and partial remission [Up to 1 year]

    Descriptive statistics will be used.

  4. Overall survival [Up to 3 years]

    Descriptive statistics will be used.

  5. Progression free survival [Up to 3 years]

    Descriptive statistics will be used.

Secondary Outcome Measures

  1. Duration of persistence of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells [Up to day 365]

    Descriptive statistics will be used.

  2. Migration of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells [Up to 1 year]

    Descriptive statistics will be used.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 CLL for whom ibrutinib is now standard first line therapy, must have progressed on ibrutinib; patients with fludarabine refractory disease are eligible; patients may be treated following allogeneic hematopoietic cell transplant (HCT); for the concurrent ibrutinib cohort, patients must agree to continue on or be restarted on ibrutinib and must not have had prior intolerance to ibrutinib that would prevent this; patients managed with prior dose reductions for toxicity will continue at the reduced dose for the remainder of this study

  • 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 or refractory ALL

  • Patients with one of the above diagnoses whose disease state does not qualify but who have prognostic indicators that suggest a high risk of progression of disease may be screened and undergo leukapheresis; enrollment for T cell therapy would require meeting the full disease state eligibility

  • 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 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 ongoing daily corticosteroid therapy at a dose of > 15 mg of prednisone per day (or equivalent); pulsed corticosteroid use for disease control is acceptable

  • 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

  • Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume in one second (FEV1) of < 50 % of predicted will be excluded

  • 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

Locations

SiteCityStateCountryPostal Code
1Fred Hutch/University of Washington Cancer ConsortiumSeattleWashingtonUnited States98109

Sponsors and Collaborators

  • Fred Hutchinson Cancer Center
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jordan Gauthier, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT01865617
Other Study ID Numbers:
  • 2639.00
  • NCI-2013-00073
  • 2639
  • RG9213011
  • P50CA107399
  • R01CA136551
First Posted:
May 31, 2013
Last Update Posted:
Feb 25, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 25, 2022