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OncoMatch/Clinical Trials/NCT03676504

Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR

Is NCT03676504 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including CD19.CAR T Cells and Fludarabine for acute lymphoblastic leukemia, adult.

Phase 1/2RecruitingUniversity Hospital HeidelbergNCT03676504Data as of May 2026

Treatment: CD19.CAR T Cells · Fludarabine · CyclophosphamideAdult patients with r/r acute lymphoblastic leukemia (ALL) (stratum I), r/r Non-Hodgkin's lymphoma (NHL) including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) or mantle cell lymphoma (MCL) (stratum II) as well as paediatric patients with r/r ALL (stratum III) will be treated with autologous T-lymphocytes transduced by the third-generation RV-SFG.CD19.CD28.4-1BBzeta retroviral vector. The main purpose of this study is to evaluate safety and feasibility of escalating CD19.CAR T cell doses (0,1-20×20\^7 transduced cells/m\^2) after lymphodepletion with fludarabine and cyclophosphamide.

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Extracted eligibility criteria

Cancer type

Acute Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Diffuse Large B-Cell Lymphoma

Non-Hodgkin Lymphoma

Biomarker criteria

Required: CD19 overexpression (confirmed CD19 expression on malignant cells in relapse)

Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL by cytology and flow cytometry (FACS)

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 2 prior lines

Must have received: chemoimmunotherapy

Relapsed or refractory disease (including "molecular relapse" with minimal residual disease (MRD) levels > 10^-3 at two occasions > 2 weeks apart) with confirmed CD19 expression on malignant cells in relapse

Must have received: Bruton's tyrosine kinase inhibitor — CLL

failure or intolerance of both Bruton's tyrosine kinase Inhibitor (BTKi) and B-cell lymphoma 2 inhibitors (BCL-2i)

Must have received: B-cell lymphoma 2 inhibitor — CLL

failure or intolerance of both Bruton's tyrosine kinase Inhibitor (BTKi) and B-cell lymphoma 2 inhibitors (BCL-2i)

Must have received: autologous stem cell transplantation — DLBCL, FL, MCL

Relapse after autologous stem cell transplantation (autoSCT)

Must have received: allogeneic stem cell transplantation — ALL, CLL, DLBCL, FL, MCL

Any relapse after allogeneic stem cell transplantation (alloSCT) (≥ 6 months from alloSCT at time of CAR T cell infusion)

Must have received: idelalisib — FL

ineligibility for or failure of idelalisib

Lab requirements

Blood counts

ANC ≥ 500/mm3; ALC ≥ 100/mm3

Kidney function

serum creatinine of ≤ 2 x ULN or eGFR ≥ 30 mL/min/1.73 m^2 (adults); serum creatinine-clearance ≥ 30 mL/min/1.73 m^2 (children)

Liver function

ALT ≤ 5 times the ULN for the respective age; Bilirubin ≤ 2.0 mg/dl (exceptions for Gilbert-Meulengracht syndrome or extrahepatic disease)

Cardiac function

Hemodynamic stability and LVEF ≥ 40% (adults); LVEF ≥ 40% or shortening fraction > 29% (children)

Adequate organ function: Renal function defined as: serum creatinine of ≤ 2 x ULN or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2; Liver function defined as: ALT ≤ 5 times the ULN for the respective age; Bilirubin ≤ 2.0 mg/dl with the exception of patients with hyperbilirubinemia explained by Gilbert-Meulengracht syndrome (may be included if total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) or extrahepatic disease (e.g. chronic hemolytic anemia); minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygenation > 90% on room air; Hemodynamic stability and left ventricular ejection fraction (LVEF) ≥ 40% as confirmed by echocardiogram; Absolute neutrophil count (ANC) ≥ 500/mm3; Absolute lymphocyte count (ALC) ≥ 100/mm3

Structured fields extracted by AI. May contain errors — verify against the official protocol.

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