NCT03893019

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for early_phase_1

Timeline
Completed

Started Mar 2019

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
terminated

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

March 6, 2019

Completed
2 days until next milestone

Study Start

First participant enrolled

March 8, 2019

Completed
19 days until next milestone

First Posted

Study publicly available on registry

March 27, 2019

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 30, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2023

Completed
Last Updated

May 16, 2024

Status Verified

May 1, 2024

Enrollment Period

3.9 years

First QC Date

March 6, 2019

Last Update Submit

May 15, 2024

Conditions

Melanoma (Skin)

Outcome Measures

Primary Outcomes (2)

  • Determination of MTD

    MTD is defined as the highest dose level at which \< 33% of patients experience dose limiting toxicity (DLT)

    Week 4 after infusion of MB-CART20.1

  • Safety and Toxicity Assessment per Adverse Event reporting classified according to CTCAE V5.0

    per Adverse Event reporting classified according to CTCAE V5.0

    until day 28 after infusion of MB-CART20.1

Secondary Outcomes (6)

  • Clinical Response

    1 year after infusion of MB-CART20.1

  • Frequency of B-cell aplasia

    1 year after infusion of MB-CART20.1

  • Phenotype and Persistence of infused MB-CART20.1

    1 year after infusion of MB-CART20.1

  • Presence and phenotype of MB-CART20.1 and B cells in biopsies

    Screening, 8 weeks after infusion of MB-CART20.1

  • Number of CD20+ tumor cells

    Screening, 8 weeks after infusion of MB-CART20.1

  • +1 more secondary outcomes

Study Arms (3)

Dose Level 1: 1x10e5 MB-CART20.1 cells

EXPERIMENTAL

3+3 patients will be treated with 1x10e5 MB-CART20.1 cells per kg body weight administered intravenously

Biological: MB-CART20.1

Dose Level 2: 1x10e6 MB-CART20.1 cells

EXPERIMENTAL

3+3 patients will be treated with 1x10e6 MB-CART20.1 cells per kg body weight administered intravenously

Biological: MB-CART20.1

Dose Level 3: 1x10e7 MB-CART20.1 cells

EXPERIMENTAL

3+3 patients will be treated with 1x10e7 MB-CART20.1 cells per kg body weight administered intravenously

Biological: MB-CART20.1

Interventions

MB-CART20.1BIOLOGICAL

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

Also known as: CD20-targeting CAR T cells, anti-CD20 CAR T cells
Dose Level 1: 1x10e5 MB-CART20.1 cellsDose Level 2: 1x10e6 MB-CART20.1 cellsDose Level 3: 1x10e7 MB-CART20.1 cells

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +5 more criteria

You may not qualify if:

  • 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
  • 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)
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Cologne - Clinic for Internal Medicine I

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Related Publications (1)

  • Aleksandrova K, Leise J, Priesner C, Aktas M, Apel M, Assenmacher M, Burger I, Richter A, Altefrohne P, Schubert C, Holzinger A, Barden M, Bezler V, von Bergwelt-Baildon M, Borchmann P, Goudeva L, Glienke W, Arseniev L, Esser R, Abken H, Koehl U. Automated manufacturing and characterization of clinical grade autologous CD20 CAR T cells for the treatment of patients with stage III/IV melanoma. Front Immunol. 2024 Sep 25;15:1328368. doi: 10.3389/fimmu.2024.1328368. eCollection 2024.

    PMID: 39386211DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Peter Borchmann, Prof.

    Universitätsklinikum Köln

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 6, 2019

First Posted

March 27, 2019

Study Start

March 8, 2019

Primary Completion

January 30, 2023

Study Completion

January 30, 2023

Last Updated

May 16, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)