Clinical Trials /

AntiCD19 Chimeric Antigen Receptor T Cells for Relapsed or Refractory Non Hodgkin Lymphoma

NCT03434769

Description:

The purpose of this study is to determine if it is possible to treat your cancer with a new type of T cell-based immunotherapy (therapy that uses your immune system to treat the cancer). T cells are a type of white blood cell that helps the body fight infections. This treatment uses T cells already present within your body that have been modified outside of the body and returned to target your cancer. This type of treatment is sometimes referred to as adoptive cell transfer (ACT). In this study the specific type of cells that will be used is called chimeric antigen receptor T cells (CAR T cells). Another purpose of this study is to learn about the side effects and toxicities related to this treatment.

Related Conditions:
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AntiCD19 Chimeric Antigen Receptor T Cells for Relapsed or Refractory Non Hodgkin Lymphoma
  • Official Title: Phase I Clinical Trial of AntiCD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CASE2417
  • NCT ID: NCT03434769

Conditions

  • Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CyclophosphamideCyclophosphamide + Fludarabine + Infusion of CAR-T Cells
FludarabineCyclophosphamide + Fludarabine + Infusion of CAR-T Cells
CAR-T CellsCyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Purpose

The purpose of this study is to determine if it is possible to treat your cancer with a new type of T cell-based immunotherapy (therapy that uses your immune system to treat the cancer). T cells are a type of white blood cell that helps the body fight infections. This treatment uses T cells already present within your body that have been modified outside of the body and returned to target your cancer. This type of treatment is sometimes referred to as adoptive cell transfer (ACT). In this study the specific type of cells that will be used is called chimeric antigen receptor T cells (CAR T cells). Another purpose of this study is to learn about the side effects and toxicities related to this treatment.

Detailed Description

      Primary Objective: To determine the safety of the treatment of relapsed or refractory B cell
      lymphomas with chimeric antigen receptor T cells targeting cluster of differentiation antigen
      19 (CD19) and to find the recommended phase II dose for this cellular therapy

      Secondary Objectives

        -  To describe the safety profile of the infusion of CAR-T cells targeting CD19.

        -  To describe the toxicities related to infusion of CAR-T cells targeting CD19.

        -  To describe the overall response rate and complete response rate of relapsed B cell
           malignancies treated with CAR-T cells targeting CD19.
    

Trial Arms

NameTypeDescriptionInterventions
Cyclophosphamide + Fludarabine + Infusion of CAR-T CellsExperimentalLymphodepletive regimen, consisting of Cyclophosphamide 60mg/kg IV on day -6 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of Chimeric antigen receptor T-cells (CAR-T) on day 0
  • Cyclophosphamide
  • Fludarabine
  • CAR-T Cells

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have relapsed or refractory non-Hodgkin lymphoma treated with at least
             two lines of therapy. Disease must have either progressed after the last regimen or
             presented failure to achieve partial or complete remission with the last regimen.

          -  The patient's lymphoma must be CD19 positive, either by immunohistochemistry or flow
             cytometry analysis on the last biopsy available.

          -  Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2

          -  Total bilirubin ≤ 1.5 times the institutional upper limit of normal

          -  Aspartate transaminase (AST or SGOT) ≤ 3 X institutional upper limit of normal

          -  Alanine transaminase (ALT or SGPT) ≤ 3 X institutional upper limit of normal

          -  Serum Creatinine ≤ 2 X the institutional upper limit of normal

          -  Subjects must have the following hematologic function parameters:

               -  absolute neutrophil count (ANC)>1,000/uL

               -  Absolute Lymphocyte Count >100/uL

               -  Platelets >50,000/uL

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Autologous transplant within 6 weeks of planned CAR-T cell infusion

          -  History of allogeneic stem cell transplant.

          -  Recipient of CAR-T cell therapy outside of this protocol.

          -  Active central nervous system or meningeal involvement by lymphoma. Subjects with
             untreated brain metastases or central nervous system (CNS) disease will be excluded
             from this clinical trial because of their poor prognosis and because they often
             develop progressive neurologic dysfunction that would confound the evaluation of
             neurologic and other adverse events. Patients with a history of CNS or meningeal
             involvement must be in a documented remission by cerebrospinal fluid evaluation and
             contrast-enhanced MRI imaging for at least 90 days prior to registration.

          -  Active malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g.
             cervix, bladder, breast).

          -  HIV seropositivity

          -  Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations
             that would limit compliance with study requirements.

          -  Pregnant or breastfeeding women are excluded from this study because CAR-T cell
             therapy may be associated with the potential for teratogenic or abortifacient effects.
             Women of child bearing potential must have a negative serum pregnancy test. Because
             there is an unknown, but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with CAR-T cells, breastfeeding should be
             discontinued. These potential risks may also apply to other agents used in this study.

          -  Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on
             any bone marrow biopsy prior to initiation of therapy

          -  Serologic status reflecting active hepatitis B or C infection. Patients that are
             positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or
             hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to
             enrollment. (PCR positive patients will be excluded.)

          -  Patients with history of clinically relevant CNS pathology such as epilepsy, seizure
             disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain
             injuries, dementia and Parkinson's disease.

          -  History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus
             erythematosus) with requirement of immunosuppressive medication within 6 months.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with Lymphoma response
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:The 2014 Lugano Response for Malignant Lymphoma will be used the following categories of response: : Complete Response (CR), Partial Response (PR), Stable Disease (SD), Relapse and Progression (PD).

Secondary Outcome Measures

Measure:Duration of response
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:This is measured, only in responders, from the documented beginning of response (CR or PR) to the time of relapse.
Measure:Disease-free survival
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:Survival is defined as the date of study entry to the date of death. Disease-free survival is measured from the time of occurrence of disease-free state to disease recurrence or death from lymphoma or acute toxicity of treatment.
Measure:Disease-specific survival
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:To minimize the risk of bias, the event should be recorded as death from lymphoma, or from toxicity from the drug. Death from unknown causes should be attributed to the drug.
Measure:Progression-free survival
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:Progression-free Survival (PFS) is defined as the time from entry onto study until lymphoma progression or death from any cause.
Measure:Time to progression
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:Time to progression (TTP) is defined as the time from study entry until lymphoma progression or death due to lymphoma.
Measure:Time to treatment failure
Time Frame:Up to 12 months after getting CAR-T infusion
Safety Issue:
Description:Time to treatment failure (event-free survival) is measured from the time from study entry to any treatment failure including discontinuation of treatment for any reason

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • Cyclophosphamide
  • Fludarabine
  • Chimeric antigen receptor T cells

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