Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR
1 other identifier
interventional
68
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2018
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 7, 2018
CompletedStudy Start
First participant enrolled
September 7, 2018
CompletedFirst Posted
Study publicly available on registry
September 18, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
July 29, 2024
July 1, 2024
8.3 years
September 7, 2018
July 26, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
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)
Up to 90 days after CD19.CAR T cell administration
Feasibility of CD19.CAR T cell manufacturing assessing the number of transduced T cells
Within 45 days prior to CD19.CAR T cell administration
Study Arms (3)
Stratum I
EXPERIMENTALAdult patients with relapsed or refractory ALL
Stratum II
EXPERIMENTALAdult patients with relapsed or refractory CLL, DLBCL, FL or MCL
Stratum III
EXPERIMENTALPediatric patients with relapsed or refractory ALL
Interventions
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
Eligibility Criteria
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
- +42 more criteria
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.
- 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
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
University Hospital Heidelberg
Heidelberg, Germany
University Hospital Heidelberg
Heidelberg, Germany
Related Publications (3)
Derigs P, Schubert ML, Dreger P, Schmitt A, Yousefian S, Haas S, Rothemeier C, Neuber B, Huckelhoven-Krauss A, Bruggemann M, Bernhard H, Kobbe G, Lindemann A, Rummel M, Michels B, Korell F, Ho AD, Muller-Tidow C, Schmitt M. Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study. Leukemia. 2024 Nov;38(11):2419-2428. doi: 10.1038/s41375-024-02392-7. Epub 2024 Aug 27.
PMID: 39192036DERIVEDSchubert ML, Schmitt A, Huckelhoven-Krauss A, Neuber B, Kunz A, Waldhoff P, Vonficht D, Yousefian S, Jopp-Saile L, Wang L, Korell F, Keib A, Michels B, Haas D, Sauer T, Derigs P, Kulozik A, Kunz J, Pavel P, Laier S, Wuchter P, Schmier J, Bug G, Lang F, Gokbuget N, Casper J, Gorner M, Finke J, Neubauer A, Ringhoffer M, Wolleschak D, Bruggemann M, Haas S, Ho AD, Muller-Tidow C, Dreger P, Schmitt M. Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. J Hematol Oncol. 2023 Jul 22;16(1):79. doi: 10.1186/s13045-023-01470-0.
PMID: 37481608DERIVEDSchubert ML, Schmitt A, Sellner L, Neuber B, Kunz J, Wuchter P, Kunz A, Gern U, Michels B, Hofmann S, Huckelhoven-Krauss A, Kulozik A, Ho AD, Muller-Tidow C, Dreger P, Schmitt M. Treatment of patients with relapsed or refractory CD19+ lymphoid disease with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector: a unicentre phase I/II clinical trial protocol. BMJ Open. 2019 May 19;9(5):e026644. doi: 10.1136/bmjopen-2018-026644.
PMID: 31110096DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Prof. Dr. Michael Schmitt
University Hospital Heidelberg, Department V
- PRINCIPAL INVESTIGATOR
Prof. Dr. Andreas Kulozik
University Hospital Heidelberg, University Medical Center for Children and Adolescents
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Head of the GMP Core Facility University Hospital Heidelberg, Principal Investigator, Clinical Professor for Cellular Immunotherapy
Study Record Dates
First Submitted
September 7, 2018
First Posted
September 18, 2018
Study Start
September 7, 2018
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2027
Last Updated
July 29, 2024
Record last verified: 2024-07