Direkt zum Inhalt | Direkt zur Navigation

Benutzerspezifische Werkzeuge

Sektionen
Studienregister
Sie sind hier: Startseite / Klinische Studien / Studienregister

Studienregister

MB-CART2019.1 Lymphoma

AcronymISRCTNEudraCTClinicaltrials.govDRKS
M-2018-3312018-001253-27

A phase I/II safety, dose finding and feasibility trial of MB-CART2019.1 in patients with relapsed or resistant CD20 and CD19 positive B-NHL

Status: Active

Purpose / Objectives

Primary Outcome

The objective of this trial is to assess feasibility, safety and efficacy of ex vivo generated MB-CART2019.1 in patients with relapsed or refractory CD20 and CD19 positive B-NHL/CLL/SLL

Part I:

Primary objective:

To assess the feasibility, safety, and toxicity of MB-CART2019.1

Secondary objective:

  • Preliminary evidence of response to treatment
  • Phenotype and persistence of MB-CART2019.1

Secondary Outcomes

Part II:

Primary objective:

To assess response to treatment of adoptive cell therapy using MB-CART2019.1 at Month 3, separately for the disease entities studied: DLBCL, MCL, FL and CLL/SLL

Secondary objective:

  • Response to treatment and duration of response.
  • Safety and toxicity assessment of MB-CART2019.1
  • Phenotype and persistence of MB-CART2019.1

 

Diagnosis

Patient attributes

Age

18-99

Inclusion criteria

Male or female patients with:

  • Refractory/relapsed CD20+ and CD19+ B-NHL (including malignant transformation like Richter’s transformation) with no curative treatment option. CD20 and CD19 positivity must be reconfirmed by FACS or immunohistochemistry at screening. Including, but not restricted to:
  • Diffuse large B cell lymphoma: relapsed/refractory disease after ASCT or ineligible for ASCT; transformation from CLL, SLL or FL allowed

  • Follicular lymphoma: at least 2 prior regimens and progression < 2 years after most recent line of therapy

  • Mantle cell lymphoma: beyond 1st CR with relapsed disease, progressive disease during first-line rituximab chemotherapy, or persistant disease after first line rituximab-chemotherapy and not eligible or appropriate for conventional therapy, ASCT or relapsed after prior autologous SCT

  • CLL and SLL: relapsed after at least one line of chemo-immunotherapy and progressed or intolerant to ibrutinib monotherapy

  • ECOG performance status of 0-2
  • Negative serological hepatitis B 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 for HCVAb, negative HIV1/2 test within 6 weeks prior to enrollment
  • 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. [...]
  • 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 of brain metastases
  • Known history or presence of clinically relevant central nervous system (CNS) pathology, such as epilepsy, paresis, aphasia, stroke within the prior 3 monts, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness or psychosis. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS
  • Patients wih history of primary immunodeficiency,
  • Patients with any history of auto-immune induced condition such as those caused by checkpoint inhibitors, MEK ihibitors or BRAF inhibitors, for examole pituitary hypophysitis must be excluded
  • Active inflammatory CNS dysfunction or meningeosis
  • Patients with Chronic Lymphocytic Leukemia unless suffering from malignant transformation
  • Active systemic fungal, viral or bacterial infection
  • Creatinine clearance calculated according to the modified formula of Cockcroft and Gault
  • 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 6 weeks before leukapheresis
  • Chemotherapy within 6 weeks prior to leukapheresis
  • Other treatment within 4 weeks or five half-lives, whichever is longer before MB-CART2019.1 infusion. This pertains to immunomodulatory therapies such as checkpoint inhibitors beause 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 hypersensivity (e.g. live vaccines and fludarabine)
  • Patients in which trail related procedures are contraindicated as judged by the investigator, e.g. lumbar pnctures for CSF 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
  • Committal to an institution on judicial or official order
  • Cerebral dysfunction, legal incapacity
  • Other investigational treatment within 4 weeks before IMP infusion
  • Clinically relevant autoimmune diseases or history of autoimmune disease
  • [..]

Trial design

  • Phase I/II
  • Multicenter
  • Prospective
  • One-arm
  • Open Label

Intervention

Leukapheresis of the patient:

  • Day -14 at the collection centre according to local standard practice.

IMP-Manufacturing: day -13 to day -1

  • The leukapheresis of the patient will be used for the individual manufacturing of MB-CART2019.1 by using the automated CliniMACS Prodigy System. CD4+ and CD8+ cells are enriched and activated, followed by lentivirus-based transduction of the LTG1497 CAR construct. Then the LTG1497 CAR transduced T cells are expanded and finally formulated.

Chemotherapy for lymphodepletion of the patient:

  • Cyclophosphamide 300 mg/m2 body surface: day -5 to -3
  • Fludarabine 30 mg/m2 body surface: days -5 to -3
  • For patients with moderate impairment of renal function, (creatinine clearance between 30 and 70 ml/min) the recommended Fludarabine dose should be reduced to 50 % and the patient’s renal functions should be monitored daily.

Experimental intervention:

  • IMP administration day 0

Control intervention: Not applicable

Duration of intervention per patient:

  • The patients will receive one infusion of the IMP in infusion solution which final volume is adapted to the patients’ weight, over a time period of approx. 15 minutes (slow intravenous infusion via a large peripheral vein or central line).

Documents (password protected)

Responsibilities in overall trial

Miltenyi Biotec GmbH

National Coordinating Investigator

Prof. Dr. med. Peter Borchmann

Study Sites

Klinik I für Innere Medizin

Study office

  • Klinisches Studienzentrum der Klinik I für Innere Medizin Köln

Status

Active

Principal Investigator

Prof. Dr. med. Peter Borchmann

Deputy of Principal Investigator

  • Prof. Dr. med. Barbara Eichhorst
  • PD Dr. Dr. med. Udo Holtick

Subinvestigator

  • Hyatt Balke-Want
  • PD Dr. med. Boris Böll
  • Dr. Philipp Gödel
  • Dr. med. Anja Jühling
  • Dr. med. Armin Tuchscherer
  • Priv.-Doz. Dr. med. Bastian von Tresckow
  • Prof. Dr. med. Dr. h. c. Christoph Scheid
  • PD Dr. med. Thomas Zander
  • Jorge Garcia Borrega
  • Dr. med. Janine Böll, geb. Schwamb
  • Dr. med. Laura Beckmann
  • Dr. med. Carmen Diana Herling
  • Dr. med. Nadine Kutsch

Contact at Site