Relapsed and/or refractory CD19+ leukemia and lymphoma MedDRA version: 21.0 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864 MedDRA version: 23.0 Level: LLT Classification code 10029595 Term: Non-Hodgkin's lymphoma NOS refractory System Organ Class: 100000004864
Conditions
Interventions
Product Name: CD19.CAR T cells
Pharmaceutical Form: Infusion
INN or Proposed INN: 3G. CD19 CAR T Cells
Current Sponsor code: HD-CAR-1
Other descriptive name: 3G. CD19 CAR T Cells
Concentration unit: m
Sponsors
University Hospital Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Stratum 1-2 (Adults): Inclusion Criteria: - Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients = 18 years - ALL: Confirmed CD19+ ALL (Philadelphia (Ph) + and Ph-) by cytology and flow cytometry (FACS) AND - Relapsed or refractory disease (incl. “molecular relapse” with min. residual disease (MRD) levels > 10-3 at two occasions > 2 weeks apart) with confirmed CD19-expression on malign. cells - Any relapse after allogeneic stem cell transplantation (alloSCT) (= 6 months from alloSCT at time of CAR TC transfusion) OR - Any relapse failing to achieve an MRD level of 90% on room air - Hemodynamic stability and LVEF = 40% as confirmed by echocardiogram - Abs. neutrophil count (ANC) = 500/mm3 - Abs. lymphocyte count (ALC) = 100/mm3 - Women of child-bearing potential (defined as all women physiolog. capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for one year following CD19.CAR TC therapy - Written informed consent must be obtained prior to any screening procedures Stratum 3 (Children and Adolescents with ALL): Inclusion Criteria: - Age of > 3 years until 10-3 at two occasions > 2 weeks apart) with confirmed CD19-expression on malign. cells - Any relapse after alloSCT (= 6 months from alloSCT at time o
Exclusion criteria
Exclusion criteria: Exclusion Criteria Stratum 1-2 (Adults): - The following medications are excluded: - Immunosuppressive medication with the exception of = 30 mg prednisolone/d or equivalent at the time of CAR TC 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 TC transfusion - Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CD19.CAR TC transfusion - 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 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 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 TC transfusion - Participation in another clinical trial at the time of screening Exclusion Criteria Stratum 3 (Children and Adolescents with ALL): - The following medications are excluded: - immunosuppressive medication with the exception of 6 weeks prior to CD19.CAR TC transfusion - 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. any life-limiting genetic disorder). Patients with Down Syndrome will not be excluded. - Any previous or concurrent malignancy. - The following exceptions do not constitute exclusion criteria: - Lymphoblastic lymphoma transformed into a CD19+ acute lymphoblastic leukemia - 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 CNS involvement 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 TC transfusion - Participation in another clinical trial at the time of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Safety: - Assessment of toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) - Assessment of frequency and grade of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) - Assessment of dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) Feasibility: - Yield of sufficient nucleated cells (NC) by leukapheresis - Successful transduction (= 15%) of CD3+ T cells (TCs) - Yield of the respective dose of transduced TCs ;Secondary Objective: Secondary - Evaluation of survival and function of chimeric antigen receptor (CAR) TCs directed against CD19 (CD19.CAR TC) in vivo - Characterization of in vivo cellular pharmakokinetics - Correlation of clinical response and number of circulating gene modified cells - Reduction of disease burden with CD19.CAR TC transfusions - 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) - Time to response (at least PR) after the CD19.CAR TC transfusion - Duration of overall response (DOR) after the CD19.CAR TC transfusion - Progression-free survival (PFS) after the CD19.CAR TC transfusion - Overall survival (OS) after the CD19.CAR TC transfusion - Correlation of B-cell depletion in vivo and response to CD19.CAR TC treatment ;Primary end point(s): Primary Safety: - Assessment of toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) - Assessment of frequency and grade of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) - Assessment of dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) Feasibility: - Yield of sufficient nucleated cells (NC) by leukapheresis - Successful transduction (= 15%) of CD3+ T cells (TCs) - Yield of the respective dose of transduced TCs ;Timepoint(s) of evalu | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary - Evaluation of survival and function of chimeric antigen receptor (CAR) TCs directed against CD19 (CD19.CAR TC) in vivo - Characterization of in vivo cellular pharmakokinetics - Correlation of clinical response and number of circulating gene modified cells - Reduction of disease burden with CD19.CAR TC transfusions - 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) - Time to response (at least PR) after the CD19.CAR TC transfusion - Duration of overall response (DOR) after the CD19.CAR TC transfusion - Progression-free survival (PFS) after the CD19.CAR TC transfusion - Overall survival (OS) after the CD19.CAR TC transfusion - Correlation of B-cell depletion in vivo and response to CD19.CAR TC treatment ;Timepoint(s) of evaluation of this end point: - End of Trial: d+28 +/- 3d (after CAR T-Cell Administration) - End of Study: d+90 +/- 3d (after CAR T-Cell Administration) | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Michael Schmitt
University Hospital Heidelberg
Outcome results
None listed