Clinical Trials /

Tisagenlecleucel In Primary CNS Lymphoma

NCT04134117

Description:

In this study, is researching the safety of tisagenlecleucel in participants with primary central nervous system lymphoma. . -The name of the study intervention is tisagenlecleucel.

Related Conditions:
  • Primary Central Nervous System Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Tisagenlecleucel In Primary CNS Lymphoma
  • Official Title: Pilot Study of Tisagenlecleucel, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, in Patients With Primary Central Nervous System Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 19-319
  • NCT ID: NCT04134117

Conditions

  • Primary CNS Lymphoma
  • Refractory Primary CNS Lymphoma
  • Relapsed Primary CNS Lymphoma

Interventions

DrugSynonymsArms
TisagenlecleucelKYMRIAHTisagenlecleucel

Purpose

In this study, is researching the safety of tisagenlecleucel in participants with primary central nervous system lymphoma. . -The name of the study intervention is tisagenlecleucel.

Detailed Description

      This research study is a Pilot Study, which is the first time investigators are examining
      this intervention in people with primary central nervous system lymphoma.

        -  The name of the study intervention is tisagenlecleucel. Tisagenlecleucel is an
           investigational treatment that uses the participants own immune cells, called T cells,
           to try to kill the cancerous cells

        -  The research study procedures include screening for eligibility and study treatment
           including, leukapheresis, evaluations, and follow up visits.

        -  The study treatment will be one day and participants will be followed for up to 2 years.

        -  It is expected that about 6 people will take part in this research study
    

Trial Arms

NameTypeDescriptionInterventions
TisagenlecleucelExperimentalStudy procedures include screening for eligibility and study treatment including, leukapheresis, evaluations, and follow up visits. - Tisagenlecleucel will be administered intravenously as a one-time rapid infusion predetermined dose following lymphodepleting chemotherapy.
  • Tisagenlecleucel

Eligibility Criteria

        Inclusion Criteria:

        Primary CNS Lymphoma in high risk elderly patients

          -  New diagnosis of primary CNS lymphoma.

          -  Voluntarily sign informed consent form(s)

          -  ≥60 years of age at the time of signing informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

          -  Have failed or are unable to tolerate definitive first-line methotrexate based therapy
             as defined by:

               -  Grade 3+ AKI and/or transaminitis preventing repeat treatment exposure and/or,

               -  Failure to achieve a complete response (per IPCG) following two cycles of first
                  line therapy,

                  --- Definitive first-line therapies must include high dose methotrexate-based
                  therapy but may also include temozolomide, high dose cytarabine, pemetrexed,
                  lenalidomide, ibrutinib and rituximab.

               -  Whole-brain irradiation, lenalidomide monotherapy and ibrutinib monotherapy are
                  considered first line therapy if patient was not eligible for methotrexate-based
                  chemotherapy at time of initial treatment but now meets study eligibility
                  criteria.

          -  Adequate absolute lymphocyte count (ALC > 500 cells/ul) within one week of apheresis.

          -  Adequate bone marrow function defined by absolute neutrophil count (ANC) >1000
             cells/mm3without growth factor support, and untransfused platelet count >50,000 mm3
             within 7 days.

          -  Left ventricular ejection fraction >40%

          -  Adequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine
             aminotransferase (ALT) <2.5 × upper limit of normal (ULN) and direct bilirubin <1.5 ×
             ULN

          -  Adequate renal function defined by creatinine clearance >30 ml/min using the
             Cockcroft-Gault formula

          -  International ratio (INR) or partial thromboplastin time (PTT) <1.5 × ULN, unless on a
             stable dose of anticoagulant for a thromboembolic event.

          -  The effects of tisagenlecleucel T cells on the developing human fetus are unknown. For
             this reason, women of child-bearing potential and men with partners of childbearing
             potential must agree to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to leukapheresis for at least 1-year post
             tisagenlecleucel infusion and until CAR T cells are no longer present by qPCR on two
             consecutive tests. Should a woman become pregnant or suspect she is pregnant while she
             or her partner is participating in this study, she should inform her treating
             physician immediately. Men with partners of childbearing potential treated or enrolled
             on this protocol must also agree to use adequate contraception prior to leukapheresis
             and until 4 months after tisagenlecleucel T cells administration.

          -  Ability and willingness to adhere to the study visit schedule and all protocol
             requirements

        Relapsed/Refractory Primary CNS Lymphoma

          -  Diagnosis of relapsed/refractory PCNSL having received at least one prior line of CNS
             directed therapy.

          -  Voluntarily sign informed consent form(s)

          -  ≥18 years of age at the time of signing informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Adequate absolute lymphocyte count (ALC > 500 cells/ul) within one week of apheresis.

          -  Adequate bone marrow function defined by absolute neutrophil count (ANC) >1000
             cells/mm3without growth factor support, untransfused platelet count >50,000 mm3, and
             untransfused hemoglobin >9 g/dL.

          -  Left ventricular ejection fraction >40%

          -  Adequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine
             aminotransferase (ALT) <2.5 × upper limit of normal (ULN) and direct bilirubin <1.5 ×
             ULN

          -  Adequate renal function defined by creatinine clearance >30 ml/min using the
             Cockcroft-Gault formula

          -  International ratio (INR) or partial thromboplastin time (PTT) <1.5 × ULN, unless on a
             stable dose of anticoagulant for a thromboembolic event.

          -  The effects of tisagenlecleucel T cells on the developing human fetus are unknown. For
             this reason, women of child-bearing potential and men with partners of childbearing
             potential must agree to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to leukapheresis for at least 1-year post
             tisagenlecleucel infusion and until CAR T cells are no longer present by qPCR on two
             consecutive tests. Should a woman become pregnant or suspect she is pregnant while she
             or her partner is participating in this study, she should inform her treating
             physician immediately. Men with partners of childbearing potential treated or enrolled
             on this protocol must also agree to use adequate contraception prior to leukapheresis
             and until 4 months after tisagenlecleucel T cells administration.

          -  Ability and willingness to adhere to the study visit schedule and all protocol
             requirements

        Inclusion Criteria for Lymphodepletion/Cell Infusion:

          -  No Active, uncontrolled, systemic bacterial, viral, or fungal infection.

          -  Adequate renal function defined by creatinine clearance >30 ml/min using the
             Cockcroft-Gault formula

        Exclusion Criteria:

          -  Prior treatment with an any investigational cellular therapy.

          -  Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine). Systemic
             steroids are allowed up to a dose of dexamethasone 4mg daily or equivalent.

          -  Ongoing systemic immunosuppression for acute and/or chronic GVH as a result of
             previous allogeneic bone marrow transplant.

          -  Significant co-morbid condition or disease which in the judgment of the Principal
             Investigator would place the subject at undue risk or interfere with the study;
             examples include, but are not limited to, cirrhotic liver disease, sepsis, and/or
             recent significant traumatic injury.

          -  Active, uncontrolled, systemic bacterial, viral, or fungal infection.

          -  Active hepatitis B or hepatitis C infection.

          -  HIV infection.

          -  Subjects with a history of class III or IV congestive heart failure or non- ischemic
             cardiomyopathy.

          -  Subjects with second malignancies if the second malignancy has required therapy in the
             last 3 years or is not in complete remission; exceptions to this criterion include
             successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or
             prostate cancer that does not require therapy other than hormonal therapy.

          -  Pregnant or lactating women

          -  Live virus vaccines within 2 weeks prior to planned start of lymphodepleting
             chemotherapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE Criteriaand ASTCT 2018 (CRS/NT)
Time Frame:12 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective disease response to tisagenlecleucel
Time Frame:1 Month
Safety Issue:
Description:IPCG response criteria.
Measure:Objective disease response to tisagenlecleucel
Time Frame:3 Months
Safety Issue:
Description:IPCG response criteria.
Measure:Objective disease response to tisagenlecleucel
Time Frame:6 months
Safety Issue:
Description:IPCG response criteria.
Measure:Objective disease response to tisagenlecleucel
Time Frame:12 months
Safety Issue:
Description:IPCG response criteria.
Measure:Overall Survival Rate
Time Frame:15 years
Safety Issue:
Description:Kaplan-Meier method
Measure:Progression Free Survival Rate
Time Frame:from the date of assignment until the date of first documented progression or date of deathfrom any cause, whichever comes first, assessed up to 100 months
Safety Issue:
Description:Kaplan-Meier method

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Matthew J. Frigault, M.D.

Trial Keywords

  • Primary CNS Lymphoma
  • Refractory Primary CNS Lymphoma
  • Relapsed Primary CNS Lymphoma

Last Updated

January 10, 2020