Clinical Trials /

MB-CART20.1 Melanoma

NCT03893019

Description:

This is a phase l multi-centric, single arm, prospective, open, dose-escalation study in patients with unresectable stage III oder IV melanoma. The trial will include 15 adult patients. The trial is a classic 3+3 design with 1 Log dose increments and maximum 3 dose levels of the intravenously administered MB-CART20.1.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MB-CART20.1 Melanoma
  • Official Title: Multicenter Phase I Trial of MB-CART20.1 for the Treatment of Patients With Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: M-2015-307
  • NCT ID: NCT03893019

Conditions

  • Melanoma (Skin)

Interventions

DrugSynonymsArms
MB-CART20.1CD20-targeting CAR T cells, anti-CD20 CAR T cellsDose Level 1: 1x10e5 MB-CART20.1 cells

Purpose

This is a phase l multi-centric, single arm, prospective, open, dose-escalation study in patients with unresectable stage III oder IV melanoma. The trial will include 15 adult patients. The trial is a classic 3+3 design with 1 Log dose increments and maximum 3 dose levels of the intravenously administered MB-CART20.1.

Detailed Description

      This Phase I trial will be the first trial with CD20 CAR transduced T cells in Europe
      targeting melanoma. The rationale for the trial is based on the finding that melanoma cancer
      sustaining cells express CD20 and that targeting CD20+ cells in preclinical model has a
      strong antitumor effect.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Level 1: 1x10e5 MB-CART20.1 cellsExperimental3+3 patients will be treated with 1x10e5 MB-CART20.1 cells per kg body weight administered intravenously
  • MB-CART20.1
Dose Level 2: 1x10e6 MB-CART20.1 cellsExperimental3+3 patients will be treated with 1x10e6 MB-CART20.1 cells per kg body weight administered intravenously
  • MB-CART20.1
Dose Level 3: 1x10e7 MB-CART20.1 cellsExperimental3+3 patients will be treated with 1x10e7 MB-CART20.1 cells per kg body weight administered intravenously
  • MB-CART20.1

Eligibility Criteria

        Inclusion Criteria:

        Male or female patients with

          -  Histologically confirmed unresectable stage III or stage IV melanoma

          -  Willingness to provide a tumor biopsy between the screening visit and prior to
             administration of the IMP and eight weeks after treatment

          -  Progressive disease despite treatment with indicated standard therapies. Time window
             for decision about progressive disease is to be made depending on the treatment
             regimen chosen.

          -  Measurable lesions according to RECIST1.1

          -  ECOG (Eastern cooperative oncology group) performance status of 0-2

          -  Negative serological hepatitis B (HBV) test defined as negative tests for HBsAg and
             HBcAb, unless serology is positive due to recent IVIG therapy, HBcAb positivity will
             be allowed if HbsAb is present, negative testing of HCVAb, negative human
             immunodeficiency virus (HIV) 1/2 test within 6 weeks prior to enrollment.

          -  Estimated life expectancy of more than 6 months

          -  At least 18 years of age

          -  WBC ≥ 2500/µL

          -  ANC ≥ 1000/µL

          -  Platelets ≥ 75 x 103/µL

          -  Hemoglobin ≥ 9 g/dL

          -  AST ≤ 3 x upper limit of normal (ULN) for patients without liver metastasis

          -  AST < 5 x ULN for patients with liver metastasis

          -  Total Bilirubin ≤ 2 x ULN

          -  patients with Gilbert's Syndrome increase of indirect bilirubin < 6mg/dL

          -  No childbearing potential (i.e. postmenopausal, absence of menstrual bleeding for at
             least 1 year, hysterectomy, bilateral ovariectomy or tubal section/ligation) or
             negative pregnancy test at screening and before chemotherapy in women with
             childbearing potential. Sexually active female patients of childbearing potential
             should use one of the following highly effective methods of contraception (Pearl index
             < 1%): hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine
             devices or systems (e.g. hormonal and non-hormonal IUD), or vasectomized sexual
             partner for at least 1 month before the trial start, during the course of the trial
             and in the 6 months following dosing. Sexual abstinence is restricted to true
             abstinence ( in line with the preferred and usual lifestyle of the subject).

          -  male patients, unless surgically sterile, must be using two acceptable methods for
             contraception (e.g. spermicide and condom) during the trial and refrain from fathering
             a child throughout the trial and for up to 12 months after dosing.

          -  Signed and dated informed consent before conduct of any trial-specific procedure.

        Exclusion Criteria:

          -  Any evidence of brain metastases

          -  CNS (central nervous system) disorders and previous strokes, if clinically relevant

          -  Patients with epilepsy

          -  Clinically relevant autoimmune disorders or history of clinically relevant autoimmune
             disorders

          -  Patients with T-cell lymphoma

          -  Treatment with anti-CD20 antibodies or checkpoint blockade inhibitors within 6 weeks
             before leukapheresis

          -  Chemotherapy within 6 weeks prior to leukapheresis

          -  History of primary immunodeficiency

          -  Creatinine clearance < 50 ml/min calculated according to the modified formula of
             Cockcroft and Gault

          -  concurrent systemic radiotherapy

          -  Use of systemic corticosteroids and immunosuppressive medication except prednisone ≤
             10 mg QD or equivalent

          -  Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial
             infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring
             ongoing treatment, unstable angina pectoris)

          -  Other investigational treatment within 4 weeks before MB-CART20.1 infusion

          -  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 related toxicities

          -  Patients in which such medication (likely to be given during trial participation) is
             contraindicated for other reasons than hypersensitivity, e.g. live vaccines and
             fludarabine.

          -  Severe pulmonary disease (DLCO and/or FEV1 < 65%, dyspnoea at rest)

          -  Active systemic fungal, viral or bacterial infection

          -  Pregnant or lactating women

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of MTD
Time Frame:Week 4 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)

Secondary Outcome Measures

Measure:Clinical Response
Time Frame:1 year after infusion of MB-CART20.1
Safety Issue:
Description:Number of patients with either Complete Response, Partial Response, Stable Disease or Progressive Disease using RECIST 1.1
Measure:Frequency 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:Phenotype and Persistence of infused 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:Presence and phenotype of MB-CART20.1 and B cells in biopsies
Time Frame:Screening, 8 weeks after infusion of MB-CART20.1
Safety Issue:
Description:Tumor biopsies for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed
Measure:Number of CD20+ tumor cells
Time Frame:Screening, 8 weeks after infusion of MB-CART20.1
Safety Issue:
Description:Tumor biopsies for determination of number of CD20+ tumor cells
Measure:Persistence of T-cell expansion for each dose group
Time Frame:Day 0 and week 12
Safety Issue:
Description:Blood samples for determination MB-CART20.1 levels (transgene copies / genomic DNA)

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Miltenyi Biomedicine GmbH

Last Updated

March 27, 2019