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

Recruiting now · Phase 1/Phase 2

Conditions studied: Acute Lymphoblastic Leukemia, Adult, Acute Lymphoblastic Leukemia, Pediatric, Chronic Lymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma

In brief

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.

Key facts

Study ID

NCT03676504

Run by

University Hospital Heidelberg

People needed

68

Starts

2018-09-07

Expected to finish

2027-12-31

Last updated by the study team

2024-07-29

Who can join

Age: 3 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Stratum I/II (Adults):
• 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
• Any relapse failing to achieve an MRD level of < 10\^-3 after ≥ 2 lines of treatment OR
• Primary refractory as defined by not achieving a complete remission (CR) after ≥ 2 lines of treatment
• CLL/NHL: Confirmed CD19+ CLL/NHL (including CLL, DLBCL, FL or MCL) with
• CLL in need of treatment with:
• Early relapse (within 2 years) after end of chemoimmunotherapy or chemoimmunotherapy refractoriness plus failure or intolerance of both Bruton's tyrosine kinase Inhibitor (BTKi) and B-cell lymphoma 2 inhibitors (BCL-2i) OR
• Relapse after alloSCT, ineligible for or refractory to standard interventions (donor lymphocyte infusions (DLI), CD20 antibodies, chemoimmunotherapy)
• DLBCL with:
• Refractoriness to a 2nd or later line of chemoimmunotherapy OR
• Relapse after autologous stem cell transplantation (autoSCT) plus ineligibility for alloSCT (including refractoriness to one line of salvage chemoimmunotherapy) OR
• Relapse after alloSCT
• FL in need of treatment with:
• Relapse <2 years after chemoimmunotherapy AND ineligibility for or failure of autologous stem cell transplantation (autoSCT) AND ineligibility for or failure of idelalisib OR
• Relapse after alloSCT, ineligible for or refractory to standard interventions (DLI, CD20 antibodies, chemoimmunotherapy)
• MCL with:
• Relapse after standard first-line therapy AND ineligibility for or failure to BTKi salvage therapy OR
• Relapse after alloSCT AND ineligibility for or failure to BTKi salvage therapy
• Measurable disease/MRD at time of enrollment
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at the time of screening
• Adequate organ function:

You may not qualify if…

• Stratum I/II (Adults):
• The following medications are excluded:
• 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
• Florid/acute or chronic Graft-versus-Host disease (GvHD)
• Uncontrolled active hepatitis B or C
• HIV-positivity
• Uncontrolled acute life-threatening bacterial, viral or fungal infection
• Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure New York Heart Association (NYHA) III-IV, uncontrolled diabetes mellitus, uncontrolled hyperlipidemia)
• Unstable angina and/or myocardial infarction within 3 months prior to screening
• Any previous or concurrent malignancy.
• The following exceptions do NOT constitute exclusion criteria:
• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
• In situ carcinoma of the cervix or breast, treated curatively without evidence of recurrence ≥ 3 years prior to the study
• CLL or FL transformed into an aggressive B cell lymphoma
• A primary malignancy which is in complete remission for ≥ 5 years
• Pregnant or nursing (lactating) women
• Intolerance to the excipients of the cell product
• Active central nervous System (CNS) involvement in ALL patient at the time of screening is not an exclusion criterion, but patients with CNS 3 status at clinical screening (d-14) are not eligible for CD19.CAR T cell transfusion
• Participation in another clinical trial at the time of screening
• Stratum III (Children and Adolescents with ALL):
• The following medications are excluded:
• immunosuppressive medication with the exception of < 0.5 mg/d*kg body weight (BW) prednisolone-equivalent at the time of CD19.CAR T cell transfusion

Where it is running

• University Hospital Heidelberg — Heidelberg, Germany (enrolling)
• University Hospital Heidelberg — Heidelberg, Germany (enrolling)

Full record on ClinicalTrials.gov

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