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

ConditionsAcute Lymphoblastic Leukemia, Adult Acute Lymphoblastic Leukemia, Pediatric Chronic Lymphocytic Leukemia Diffuse Large B Cell Lymphoma Follicular Lymphoma Mantle Cell Lymphoma

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age3+

SponsorUniversity Hospital Heidelberg

About this trial

Adult 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients ≥ 18 years

ALL (Ph+ and Ph-): Confirmed CD19+ ALL by cytology and flow cytometry (FACS) AND

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

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

Disqualifiers

Immunosuppressive medication with the exception of ≤ 30 mg prednisolone/d or equivalent at the time of CAR T cell transfusion

Bridging/maintenance therapy including chemo- and immunotherapy must be stopped ≥ 2 weeks prior to leukapheresis, but can be continued between leukapheresis and lymphodepletion

Intrathecal chemotherapy is possible at any time, but not during lymphodepletion until 14 days after CD19.CAR T cell transfusion

Any DLI must be completed > 6 weeks prior to CD19.CAR T cell infusion

Trial design

Design model

Parallel

Treatments tested in this trial

CD19.CAR T Cells
Biological/Vaccine
Dose Level 1: 1×10\^6 transduced cells/m\^2; Dose Level 2: 5×10\^6 transduced cells/m\^2; Dose Level 3: 20×10\^6 transduced cells/m\^2; Dose Level 4: 5x10\^7 transduced cells/m\^2; Dose Level 5: 10x10\^7 transduced cells/m\^2; Dose Level 6: 20x10\^7 transduced cells/m\^2
Fludarabine
Drug
3 days of fludarabine 30 mg/m\^2/day
Cyclophosphamide
Drug
3 days of cyclophosphamide 500 mg/m\^2/day

Treatment groups

68 Participants

are divided into 3 treatment groups

Group A: Stratum IExperimental treatment 3 interventions

Group B: Stratum IIExperimental treatment 3 interventions

Group C: Stratum IIIExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

Safety of CD19.CAR T cell administration assessing grade and frequency of toxicities including cytokine release syndrome (CRS) and neurotoxicity according to Common Toxicity Criteria for Adverse Events (CTCAE)

Time frame

Up to 90 days after CD19.CAR T cell administration

Feasibility of CD19.CAR T cell manufacturing assessing the number of transduced T cells

Time frame

Within 45 days prior to CD19.CAR T cell administration

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Hospital Heidelberg

Lead sponsor

Source ClinicalTrials.gov

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