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About
This is a multi-center, phase II study to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory DLBCL.
Full description
This was a single arm, open-label, multi-center, Phase II study conducted to determine the efficacy and safety of tisagenlecleucel in adult patients with r/r DLBCL. The study consisted of the following sequential periods: Screening, Pre-Treatment, Treatment and Primary follow-up, Secondary follow-up, Survival follow-up.
Patients were enrolled in 2 cohorts to receive one tisagenlecleucel infusion as follows:
The study enrolled adult patients ≥ 18 years with histologically confirmed relapsed or refractory (r/r) DLBCL after ≥ 2 lines of chemotherapy, with a life expectancy of ≥ 12 weeks and not eligible or not consenting to stem cell transplantation (SCT).
Patients had measurable disease at time of enrollment, adequate organ function and zero or one Eastern Cooperative Oncology Group performance status at screening. For each patient, the apheresis product of non-mobilized cells was received and accepted by the manufacturing site.
Enrollment
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Volunteers
Inclusion criteria
Written informed consent must be obtained prior to any screening procedures
Histologically confirmed DLBCL at last relapse(by central pathology review before enrolment.
.- Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT
Measurable disease at time of enrollment
Life expectancy ≥12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening
Adequate organ function:
Renal function defined as:
Liver function defined as:
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air
Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)
Adequate bone marrow reserve without transfusions defined as:
Must have an apheresis product of non-mobilized cells accepted for manufacturing
Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for at least 12 months following CTL019 infusion and until CAR T cells are no longer present by PCR on two consecutive tests
Exclusion criteria
Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
Treatment with any prior gene therapy product
Active Central Nervous System (CNS) involvement by malignancy
Prior allogeneic HSCT
Eligible for and consenting to HSCT
Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
Investigational medicinal product within the last 30 days prior to screening
The following medications are excluded:
Short acting drugs used to treat leukemia or lymphoma (e.g. tyrosine kinase inhibitors, and hydroxyurea) must be stopped > 72 hour prior to leukapheresis and > 72 hours prior to CTL019 infusion
Other cytotoxic drugs, including low dose daily or weekly maintenance chemotherapy, must not be given within 2 weeks prior to leukapheresis and within 2 weeks prior to CTL019 infusion
Fludarabine may be associated with prolonged lymphopenia. This should be taken into consideration when evaluating the optimal timing for leukapheresis collection.
Prior radiation therapy within 2 weeks of infusion
Active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive )
HIV positive patients
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 6 months prior to screening
Previous or concurrent malignancy with the following exceptions:
Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 24 hours before lymphodepletion
Intolerance to the excipients of the CTL019 cell product
Cardiac arrhythmia not controlled with medical management
Prior treatment with any adoptive T cell therapy
Patients with T-cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV positive DLBCL of the elderly, Richter's transformation, and Burkitt lymphoma
Patients with active neurological auto immune or inflammatory disorders (e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)
Primary purpose
Allocation
Interventional model
Masking
115 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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