NCT03664635

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2018

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

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 3, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 10, 2018

Completed
15 days until next milestone

Study Start

First participant enrolled

September 25, 2018

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 17, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 17, 2024

Completed
Last Updated

November 21, 2024

Status Verified

November 1, 2024

Enrollment Period

6 years

First QC Date

September 3, 2018

Last Update Submit

November 19, 2024

Conditions

Relapsed or Refractory B-cell Non-Hodgkin's LymphomaNon-Hodgkin's LymphomaB-cell Lymphoma RefractoryB-cell Lymphoma Recurrent

Outcome Measures

Primary Outcomes (2)

  • Phase I - Determination of the maximum tolerated dose (MTD)

    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.

    until day 28 after infusion of MB-CART20.1

  • Phase II - Best overall response rate

    Response (Complete response (CR), Partial response (PR), Stable disease (SD), Progressive disease (PD)) is defined according to Cheson criteria.

    3 months after infusion of MB-CART20.1

Secondary Outcomes (13)

  • Phase I - Related safety and toxicity of MB-CART20.1

    months 3, 6, 9 and 12 after infusion of MB-CART20.1

  • Phase I - Best overall response rate over 4 weeks and 3 months

    4 weeks and 3 months after infusion of MB-CART20.1

  • Phase I - Best overall response rate over 1 year

    1 year after infusion of MB-CART20.1

  • Phase I - Occurrence of B-cell aplasia

    1 year after infusion of MB-CART20.1

  • Phase I - Phenotype and Persistence of MB-CART20.1

    1 year after infusion of MB-CART20.1

  • +8 more secondary outcomes

Study Arms (4)

Phase I - Safety Dose Level

EXPERIMENTAL

In 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

Biological: MB-CART20.1

Phase I - Dose Level 1

EXPERIMENTAL

In 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

Biological: MB-CART20.1

Phase I - Dose Level 2

EXPERIMENTAL

In 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

Biological: MB-CART20.1

Phase II

EXPERIMENTAL

The 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

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 in NHL

Also known as: CD20-targeting CAR T Cells, Anti-CD20 CAR T cells
Phase I - Dose Level 1Phase I - Dose Level 2Phase I - Safety Dose LevelPhase II

Eligibility Criteria

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

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University Hospital of Cologne - Clinic for Internal Medicine I

Cologne, 50937, Germany

Location

Universitätsklikum Leipzig, AöR

Leipzig, Germany

Location

MeSH Terms

Conditions

RecurrenceLymphoma, B-CellLymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Peter Borchmann, Prof. Dr.

    Universitätsklinikum Köln

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

September 3, 2018

First Posted

September 10, 2018

Study Start

September 25, 2018

Primary Completion

September 17, 2024

Study Completion

September 17, 2024

Last Updated

November 21, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will not share

Locations

DE(2)