Tisagenlecleucel In Primary CNS Lymphoma

Pilot Study of Tisagenlecleucel, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, in Patients With Primary Central Nervous System Lymphoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary CNS Lymphoma; Refractory Primary CNS Lymphoma; Relapsed Primary CNS Lymphoma
• Intervention / Treatment: Biological: 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

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Matthew J. Frigault, MD; Phone Number: (617) 643-6175; Email: mfrigault@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tisagenlecleucel; Study 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.	Biological: Tisagenlecleucel; One time single predetermined dose level CAR-positive T cells will be utilized based on the FDA approved product label.; Other Names: KYMRIAH

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective disease response to tisagenlecleucel	IPCG response criteria.	1 Month
Objective disease response to tisagenlecleucel	IPCG response criteria.	3 Months
Objective disease response to tisagenlecleucel	IPCG response criteria.	6 months
Objective disease response to tisagenlecleucel	IPCG response criteria.	12 months
Overall Survival Rate	Kaplan-Meier method	15 years
Progression Free Survival Rate	Kaplan-Meier method	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

Collaborators and Investigators

• Sponsor: Matthew J. Frigault, M.D.
• Collaborators: Novartis
• Investigators: Principal Investigator: Matthew J. Frigault, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2019
• Primary Completion (Actual): December 11, 2021
• Study Completion (Estimated): December 11, 2024

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Primary CNS Lymphoma; Refractory Primary CNS Lymphoma; Relapsed Primary CNS Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tisagenlecleucel
• Other Study ID Numbers: 19-319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No