T LYMPHOCYTES TRANSDUCED WITH A RV-SFG.CD19.CD28.4-1BBZETA RETROVIRAL VECTOR for Acute lymphoblastic leukemia (relapsed/recurrent)|Non-Hodgkin's lymphoma (refractory)|Chronic lymphocytic leukemia (CLL)|Diffuse large B-cell lymphoma (DLBCL)|Follicular lymphoma (FL)|Mantle cell lymphoma (MCL)

Inclusion criteria

• {"criterion_text":"- Stratum 1-2 (Adults): Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients ≥ 18 years"}
• {"criterion_text":"- Stratum 1-2 (Adults): Relapsed or refractory disease (including “molecular relapse” with minimal residual disease (MRD)"}
• {"criterion_text":"- Stratum 1-2 (Adults): Renal function defined as: serum creatinine of ≤ 2 x ULN or eGFR ≥ 30 mL/min/1.73 m²"}
• {"criterion_text":"- Stratum 1-2 (Adults): Absolute lymphocyte count (ALC) ≥ 100/mm³"}
• {"criterion_text":"- Stratum 3: Age of > 3 years until < 18 years at the time of screening"}
• {"criterion_text":"- Stratum 3: CD19+ ALL (Ph+ and Ph-) confirmed by cytology and flow cytometry (FACS) AND Relapsed or refractory disease"}
• {"criterion_text":"- Stratum 3: Measurable disease/MRD at time of enrollment"}
• {"criterion_text":"- Stratum 3: Life expectancy ≥ 12 weeks"}
• {"criterion_text":"- Stratum 3: ECOG performance status ≤ 2 (age ≥ 16 years) or Lansky performance status ≥ 50 (age < 16 years) at the time of screening"}
• {"criterion_text":"- Stratum 3: Renal function defined as serum creatinine-clearance ≥ 30 mL/min/1.73 m²"}
• {"criterion_text":"- Stratum 3: Absolute lymphocyte count (ALC) ≥ 100/mm³"}

Exclusion criteria

• {"criterion_text":"- Stratum 1-2 (Adults): Immunosuppressive medication with the exception of ≤ 30 mg prednisolone/d or equivalent at the time of CAR TC transfusion"}
• {"criterion_text":"- Stratum 1-2 (Adults): Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CD19.CAR TC transfusion"}
• {"criterion_text":"- Stratum 1-2 (Adults): Florid/acute or chronic Graft-versus-Host disease (GvHD)"}
• {"criterion_text":"- Stratum 1-2 (Adults): Uncontrolled acute life-threatening bacterial, viral or fungal infection"}
• {"criterion_text":"- Stratum 1-2 (Adults): A primary malignancy which is in complete remission for ≥ 5 years"}
• {"criterion_text":"- Stratum 1-2 (Adults): Pregnant or nursing (lactating) women"}
• {"criterion_text":"- Stratum 3: immunosuppressive medication with the exception of < 0.5 mg/d*kg BW prednisolone-equivalent at the time of CD19.CAR TC transfusion"}
• {"criterion_text":"- Stratum 3: Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CD19.CAR TC transfusion"}
• {"criterion_text":"- Stratum 3: Florid/acute or chronic Graft-versus-Host disease (GvHD)"}
• {"criterion_text":"- Stratum 3: Uncontrolled acute life-threatening bacterial, viral or fungal infection"}

Primary endpoints

• {"endpoint_text":"- Assessment of toxicities according to the CTCAEv5.0","definition_or_measurement_approach":"Toxicities graded using CTCAE version 5.0"}
• {"endpoint_text":"- Assessment of frequency and grade of CRS and/or ICANS","definition_or_measurement_approach":"Frequency and grading of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as assessed per study-defined criteria (frequency and grade)"}
• {"endpoint_text":"- Assessment of dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)","definition_or_measurement_approach":"Identification of DLTs and determination of MTD during dose escalation"}
• {"endpoint_text":"- Yield of sufficient NCs by leukapheresis","definition_or_measurement_approach":"Measurement of nucleated cell (NC) yield from leukapheresis sufficient for manufacturing"}
• {"endpoint_text":"- Successful transduction (>15%) of CD3+ TCs","definition_or_measurement_approach":"Transduction efficiency measured as percentage of CD3+ T cells successfully transduced; success defined as >15%"}
• {"endpoint_text":"- Yield of the respective dose of transduced TCs (1 to 20x106 transduced CD3+TCs/m2) in the first three dose levels (I-III)","definition_or_measurement_approach":"Manufacturing yield of transduced CD3+ T cells in dose levels I-III, target range 1 to 20 x 10^6 transduced CD3+ TCs per m2"}
• {"endpoint_text":"- Yield of the respective dose of transduced TCs (5 to 20x107 transduced CD3+ TCs/m2) in the second three dose levels (IV-VI)","definition_or_measurement_approach":"Manufacturing yield of transduced CD3+ T cells in dose levels IV-VI, target range 5 to 20 x 10^7 transduced CD3+ TCs per m2"}

Secondary endpoints

• {"endpoint_text":"- Evaluation of survival and function of chimeric antigen receptor (CAR) TCs directed against CD19 (CD19.CAR TC) in vivo","definition_or_measurement_approach":""}
• {"endpoint_text":"- Characterization of in vivo cellular pharmakokinetics","definition_or_measurement_approach":""}
• {"endpoint_text":"- Correlation of clinical response and number of circulating gene modified cells","definition_or_measurement_approach":""}
• {"endpoint_text":"- Reduction of disease burden with CD19.CAR TC transfusions","definition_or_measurement_approach":""}
• {"endpoint_text":"- Anti-tumor efficacy of CD19.CAR TCs in patients with CD19+ lymphoid disease (overall response rate (ORR), complete response (CR), partial response (PR)) at day 90 (EOS) after CD19.CAR TC transfusion)","definition_or_measurement_approach":"Overall response rate (ORR), CR and PR assessed at day 90 (end of study visit) after CAR TC transfusion"}
• {"endpoint_text":"- Time to response (at least PR) after the CD19.CAR TC transfusion","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of overall response (DOR) after the CD19.CAR TC transfusion","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival (PFS) after the CD19.CAR TC transfusion","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS) after the CD19.CAR TC transfusion","definition_or_measurement_approach":""}
• {"endpoint_text":"- Correlation of B-cell depletion in vivo and response to CD19.CAR TC treatment","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

16-09-2024

Latest Decision Or Authorization Date

19-09-2024

Processing Time Days

3

Number Of Sites

2

Number Of Participants

63

Primary sponsor

Full Name

Universitaetsklinikum Heidelberg AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany