A Phase II, single arm, multicenter open label trial to determine the efficacy and safety of tisagenlecleucel (CTL019) in adult patients with refractory or relapsed follicular lymphoma

Non-Hodgkin lymphomas (NHLs) comprise a heterogeneous group of lymphoid
malignancies, including immature lymphoid neoplasms, mature B-cell neoplasms,
mature T-cell and NK-cell neoplasms, and post-transplant lymphoproliferative
disorders. Mature B-cell lymphomas are further classified into indolent
lymphomas, e.g. follicular lymphoma (FL), and aggressive lymphomas, e.g.
diffuse large B-cell lymphoma (DLBCL).
FL is the second most common histologic NHL subtype in the Western hemisphere.
The estimated number of new cases in the US was 13,960 in 2016 (Teras et al
2016). Most patients are diagnosed during the sixth decade of their life but
approximately 25% of patients are 40 years of age or younger. The translocation
t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma, which results
in the constitutive overexpression of B-cell lymphoma 2 protein (Bcl-2). FL
cells also express surface immunoglobulins, B-cell lymphoma 6 protein (Bcl-6),
and B-cell associated antigens such as CD10, CD19, CD20, and CD22. FL is
classified histologically into three grades based on the number of
centroblasts.

This study has been transitioned to CTIS with ID 2023-508127-13-00 check the CTIS register for the current data.

This single arm, multi-center, phase II study will determine the efficacy and
safety of tisagenlecleucel in adult patients with FL who failed at least 2
prior systemic therapies, including an anti-CD20 antibody (e.g. rituximab) and
an alkylating agent.

Single arm, multi-center, phase II study that investigates the efficacy and
safety of tisagenecleucel in patients with follicular lymphoma patients who are
refractory or relapsed after multiple therapies. Patients are screened and the
leukapheresis takes place during screening. The cells obtained in leukapheresis
are genetically modified into the tisagenecleucel therapy. After screening,
patients are treated with lymphodepleting chemotherapy (Fludarabine in
combination with Cyclophosphamide or Bendamustine). Tisagenlecleucel is then
administered. The study continues until the last infused patient has been
followed for 24 months or previously stopped the study.

Leukapheresis, lymphodepleting chemotherapy and tisagenlecleucel infusion.

Risks: side effects may occur after the tisagenlecleucel infusion, the
leukapheresis procedure, lymphodepleting chemotherapy, and after study
procedures such as bone marrow puncture, PET-CT scan, MUGA, blood collection,
tumor biopsy, and lumbar puncture.

Burden: Leukapheresis procedure, lymphodepleting chemotherapy,tisagenlecleucel
infusion, possible hospitalization D1 - D21 (depending on medical condition), 9
controls in the first 28 days after infusion, and at least 10 visits thereafter
(depending on when the last one patient has reached the 24-month follow-up).

Physical examination: 6x in the first 28 days, then with each subsequent visit.
Blood tests: an average of 50ml, a maximum of 75ml per visit.
Leukapheresis: 1 time
Lymphodepleting chemotherapy: 1 time (2 to 6 days prior to infusion
tisagenlecleucel)
CT / MRI: month 9, month 12, and every six months thereafter.
MUGA / Echo: screening
ECG: screening and day 1 (infusion)
PET-CT: screening, 4 weeks to 8 days prior to infusion, month 3 and month 6
CT / MRI: Month 9, month 12, month 18 and month 24 and every half year
thereafter.
Bone marrow biopsy: screening, month 3 and if a complete response is achieved
and the disease was in bone marrow when screened
Lumbar puncture: if clinically indicated
Tumor biopsy: screening and after month 3 if clinically indicated
Questionnaires: screening, and every study visit after month 3.
Optional use of body material (blood and tissues) and anonymous data for future
research.