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CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03068416
Recruitment Status : Completed
First Posted : March 1, 2017
Last Update Posted : October 20, 2021
Sponsor:
Collaborators:
Uppsala University Hospital
AFA Insurance
Information provided by (Responsible Party):
Uppsala University

Brief Summary:
Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy.

Condition or disease Intervention/treatment Phase
B-cell Leukemia B-Cell Lymphoma Biological: CAR T cells Phase 2

Detailed Description:

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Primary outcome:

- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events.

Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Secondary outcome:

Tumor response, CAR T cell persistence and immunological profile

  • Determination of tumor size and the tumor marker CD19.
  • Determination of the levels of circulating B cells.
  • Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies.
  • Determination of activation markers on CAR T cells such as CD107a.
  • Determination of the presence of immunological markers in blood and biopsies.

At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy - a Phase II Trial.
Actual Study Start Date : September 18, 2017
Actual Primary Completion Date : August 19, 2021
Actual Study Completion Date : August 19, 2021


Arm Intervention/treatment
Experimental: CAR T cells
Autologous 3rd generation CD19-targeting CAR T cells
Biological: CAR T cells
Autologous CD19-targeting, 3rd generation CAR T cells




Primary Outcome Measures :
  1. Safety [ Time Frame: 24 months ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0


Secondary Outcome Measures :
  1. Tumor response [ Time Frame: 24 months. ]
    Determination of tumor size

  2. B cell levels [ Time Frame: 24 months ]
    Determination of circulating CD19+ B cells

  3. CAR T cell persistence [ Time Frame: 24 months ]
    Determination of the level of CAR T cells

  4. Immunological profile [ Time Frame: 24 months ]
    Determination of frequencies of immune cells in patient blood and tissues

  5. Cytokine profile [ Time Frame: 24 months ]
    Determination of cytokine profile in patient blood



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Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Relapsed or refractory CD19+ B-cell lymphoma or leukemia with no other curative treatment option available.
  2. Measurable disease.
  3. All ages
  4. Performance status ECOG 0-2.
  5. Fertile females/males must consent to use contraceptives during participation of the trial.
  6. Signed informed consent.

Exclusion Criteria:

  1. Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
  2. Patients with primary CNS lymphoma.
  3. Known human immunodeficiency virus (HIV) infection.
  4. Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
  5. Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to perform the treatment.
  6. Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half-lives of that drug, which is longest.
  7. Pregnancy
  8. Patients that do not consent to that tissue and blood samples are stored in a biobank
  9. Patients whose cells cannot be manufactured.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03068416


Locations
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Sweden
Uppsala University Hospital, Dept of Oncology
Uppsala, Sweden, 75185
Sponsors and Collaborators
Uppsala University
Uppsala University Hospital
AFA Insurance
Investigators
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Principal Investigator: Gunilla Enblad, MD, PhD Uppsala University Hospital, Dept of Oncology
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Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT03068416    
Other Study ID Numbers: 004:TCELL
2016-004043-36 ( EudraCT Number )
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: October 20, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia