Clinical Trials /

MB-CART20.1 Lymphoma

NCT03664635

Description:

This trial is a phase I/II trial to assess safety, dose finding and feasibility of ex vivo generated MB-CART20.1 cells in patients with relapsed or refractory CD20 positive B-NHL.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MB-CART20.1 Lymphoma
  • Official Title: A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART20.1 in Patients With Relapsed or Resistant CD20 Positive B-NHL

Clinical Trial IDs

  • ORG STUDY ID: M-2016-312
  • NCT ID: NCT03664635

Conditions

  • Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
  • Refractory/Relapsed CD20+ B-NHL

Interventions

DrugSynonymsArms
MB-CART20.1CD20-targeting CAR T Cells, Anti-CD20 CAR T cellsPhase I - Safety Dose Level

Purpose

This trial is a phase I/II trial to assess safety, dose finding and feasibility of ex vivo generated MB-CART20.1 cells in patients with relapsed or refractory CD20 positive B-NHL.

Detailed Description

      MB-CART20.1 consists of autologous Anti-CD20 Chimeric Antigen Receptor (CAR) transduced CD4
      /CD8 enriched T cells targeting CD20-positive tumor cells in Non-Hodgkin-Lymphoma (NHL)
    

Trial Arms

NameTypeDescriptionInterventions
Phase I - Safety Dose LevelExperimentalIn phase I three (3) + 3 patients will be treated with 1x10^5 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the preceding safety dose level
    Phase I - Dose Level 1ExperimentalIn phase I six (6) + 3 patients will be treated with 1x10^6 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the dose level 1
      Phase I - Dose Level 2ExperimentalIn phase I six (6) + 3 patients will be treated with 3x10^6 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the dose level 2
        Phase IIExperimentalThe number of additional patients who will be treated with MB-CART20.1 cells in Phase II is depending on the number of evaluable patients treated with the maximum tolerated dose (MTD) level and the results in Part I

          Eligibility Criteria

                  Inclusion Criteria:
          
                    -  Refractory/relapsed CD20+ B-NHL (including malignant transformation like Richter's
                       transformation) with no curative treatment option.
          
                    -  At least 18 years of age
          
                    -  Estimated life expectancy of more than 3 months
          
                    -  ECOG performance status (Eastern cooperative oncology group) of 0-2
          
                    -  Negative serological HBV (Hepatitis B virus) test, negative testing of HCVAb
                       (Hepatitis C virus Antibody), negative HIV1/2 (Human immunodeficiency virus 1/2 ) test
                       within 6 weeks prior to enrollment
          
                    -  No childbearing potential or negative pregnancy test at screening and before
                       chemotherapy in women with childbearing potential.
          
                    -  Signed and dated informed consent before conduct of any trial-specific procedure
          
                  Exclusion Criteria:
          
                    -  Participation in another interventional trial that could interact with this trial
          
                    -  Any evidence 0f CNS (Central nervous system) involvement
          
                    -  Known history or presence of clinically relevant CNS pathology
          
                    -  Patients with history of primary immunodeficiency,
          
                    -  Patients with any history of auto-immune induced condition such as those caused by
                       checkpoint inhibitors, MEK inhibitors or BRAF inhibitors, for example pituitary
                       hypophysitis must be excluded
          
                    -  Patients with Chronic Lymphocytic Leukemia unless suffering from malignant
                       transformation
          
                    -  Active systemic fungal, viral or bacterial infection
          
                    -  Serious cardiac functional incapacity (class III or IV as defined by the New York
                       Heart Association Classification)
          
                    -  Severe pulmonary disease (DLCO (Transfer factor of the lung for carbon monoxide)
                       and/or FEV1 (Forced expiratory volume in 1 second) < 65%, dyspnea at rest)
          
                    -  Liver dysfunction as indicated by a total bilirubin, AST (Aspartate Aminotransferase),
                       and ALT (Alanine aminotransferase) ≥ 2 the institutional ULN (Upper limit of normal)
                       value, unless directly attributable to the patient's tumor
          
                    -  Creatinine clearance <50 ml/min calculated according to the modified formula of
                       Cockcroft and Gault
          
                    -  Pregnant or lactating women
          
                    -  Active secondary malignancy requiring treatment (except basal cell carcinoma or
                       malignant tumor curatively treated by surgery) within the last 5 years before
                       enrollment.
          
                    -  Medical condition requiring prolonged use of systemic corticosteroids (> 1 month)
          
                    -  Prior therapy with genetically modified substances
          
                    -  Use of anti-CD20 antibodies within 4 weeks before leukapheresis
          
                    -  Chemotherapy within 4 weeks prior to leukapheresis
          
                    -  Other treatment within 4 weeks or two half-lives, whichever is longer before
                       MB-CART20.1 infusion. This pertains to immunomodulatory therapies such as checkpoint
                       inhibitors because of the influence on the immune system
          
                    -  Concurrent systemic radiotherapy
          
                    -  Hypersensitivity against any drug or its ingredients/impurities that is scheduled or
                       likely to be given during trial participation e.g. as part of the mandatory
                       lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage
                       therapies for treatment of related toxicities
          
                    -  Patients in which such medication is contraindicated for other reasons than
                       hypersensitivity (e.g. live vaccines and fludarabine)
          
                    -  Patients in which trial related procedures are contraindicated as judged by the
                       investigator, e.g. lumbar punctures for CSF (Cerebrospinal fluid) sampling
          
                    -  Patient's lack of accountability, inability to appreciate the nature, meaning and
                       consequence of the trial and to formulate his/her own wishes correspondingly
          
                    -  Patients who have a relationship of dependence or employer employee relationship to
                       the sponsor or the investigator
          
                    -  Committal to an institution on judicial or official order
          
                    -  Cerebral dysfunction, legal incapacity
          
                    -  Other investigational treatment within 4 weeks before IMP (Investigational Medicinal
                       Product) infusion
          
                    -  Clinically relevant autoimmune diseases or history of autoimmune disease
                
          Maximum Eligible Age:N/A
          Minimum Eligible Age:18 Years
          Eligible Gender:All
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure:Phase I - Determination of the maximum tolerated dose (MTD)
          Time Frame:until day 28 after infusion of MB-CART20.1
          Safety Issue:
          Description:MTD is defined as the highest dose level at which < 33% of patients experience Dose Limiting Toxicity (DLT). Safety and toxicity assessment of MB-CART20.1 per adverse events (AE) reporting classified according to CTCAE version 5.0.

          Secondary Outcome Measures

          Measure:Phase I - Related safety and toxicity of MB-CART20.1
          Time Frame:months 3, 6, 9 and 12 after infusion of MB-CART20.1
          Safety Issue:
          Description:Per adverse events (AE) reporting classified according to CTCAE version 5.0.
          Measure:Phase I - Best overall response rate over 4 weeks and 3 months
          Time Frame:4 weeks and 3 months after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase I - Best overall response rate over 1 year
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase I - Occurrence of B-cell aplasia
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.
          Measure:Phase I - Phenotype and Persistence of MB-CART20.1
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.
          Measure:Phase II - Best overall response rate over 1 year
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase II - Overall response rate over 4 weeks and 3 months
          Time Frame:4 weeks and 3 months after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase II - Overall response rate over 1 year
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase II - Number of patients with CR, PR, SD and PD
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase II -Percentage of patients with CR, PR, SD and PD
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Response (CR, PR, SD and PD) is defined according to Cheson criteria.
          Measure:Phase II - Safety and toxicity assessment of MB-CART20.1
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Per adverse events (AE) reporting classified according to CTCAE version 5.0.
          Measure:Phase II - Occurrence of B-cell aplasia
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.
          Measure:Phase II - Phenotype and Persistence of MB-CART20.1
          Time Frame:1 year after infusion of MB-CART20.1
          Safety Issue:
          Description:Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.

          Details

          Phase:Phase 1/Phase 2
          Primary Purpose:Interventional
          Overall Status:Not yet recruiting
          Lead Sponsor:Miltenyi Biotec GmbH

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