Long-Term Follow-up of Patients Treated with Miltenyi Cell and Gene Therapies

2022-501648-14-00 Protocol M-2022-393 Phase I and Phase II (Integrated) - Other Ongoing, recruiting

Start 5 May 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 9 sites · Protocol M-2022-393

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ongoing, recruiting
Participants planned 40
Countries 1
Sites 9

Relapsed or refractory CD19 positive B cell malignancies (adult ALL, adult NHL/chronic lymphatic leukemia [CLL])

To evaluate long-term safety after treatment with Miltenyi CAR T cell therapy

Key facts

Sponsor
Miltenyi Biomedicine GmbH
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Skin and Connective Tissue Diseases [C17]
Trial duration
5 May 2024 → ongoing
Decision date (initial)
2023-11-17
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Miltenyi Biomedicine GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate long-term safety after treatment with Miltenyi CAR T cell therapy

Secondary objectives 2

  1. To further assess safety concerning blood count, growth and development of pediatric patients and occurrence of replication competent lentivirus after Miltenyi CAR T cell therapy
  2. To evaluate long-term treatment efficacy of surviving patients as measured by status of disease progression and survival status over time and to evaluate persistence of the transgene

Conditions and MedDRA coding

Relapsed or refractory CD19 positive B cell malignancies (adult ALL, adult NHL/chronic lymphatic leukemia [CLL])

VersionLevelCodeTermSystem organ class
21.0 LLT 10063625 Acute lymphoblastic leukemia recurrent 10029104
20.0 LLT 10027152 Melanoma of skin (malignant) 10029104
21.0 PT 10003902 B-cell lymphoma recurrent 100000004864
21.0 PT 10003903 B-cell lymphoma refractory 100000004864
21.1 LLT 10008978 Chronic lymphocytic leukemia refractory 10029104
21.1 LLT 10008977 Chronic lymphocytic leukemia recurrent 10029104

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2018-001253-27 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, Étude de phase I/II sur la sécurité d’emploi, la détermination de dose et la faisabilité du MB-CART2019.1 chez des patients atteints de LNH à lymphocytes B récidivant ou résistant, Un estudio de fase I/II con MB-CART2019.1 para evaluar la seguridad, factibilidad y hallazgo de dosis en pacientes con LNHB recurrente o refractario
2017-000121-12 A phase I/II safety, dose finding and feasibility trial of MB-CART20.1 in patients with relapsed or resistant CD20 positive B-NHL, Eine Phase-I/II-Studie mit MB-CART20.1 zur Beurteilung der Sicherheit und Machbarkeit sowie zur Dosisfindung bei Patienten mit wiederkehrenden oder resistenten CD20 positiven B-Zell Non-Hodgkin-Lymphomen (B-NHL)., Eine Phase-I/II-Studie mit MB-CART20.1 zur Beurteilung der Sicherheit und Machbarkeit sowie zur Dosisfindung bei Patienten mit wiederkehrenden oder resistenten CD20 positiven B-Zell Non-Hodgkin-Lymphomen (B-NHL)., Eine Phase-I/II-Studie mit MB-CART20.1 zur Beurteilung der Sicherheit und Machbarkeit sowie zur Dosisfindung bei Patienten mit wiederkehrenden oder resistenten CD20 positiven B-Zell Non-Hodgkin-Lymphomen (B-NHL).
2017-002848-32 A phase I/II safety, dose finding and feasibility trial of MB-CART19.1 in patients with relapsed or refractory CD19 positive B cell malignancies., Eine Phase-I/II-Studie mit MB-CART19.1 zur Beurteilung der Sicherheit und Machbarkeit sowie zur Dosisfindung bei Patienten mit wiederkehrenden oder therapie-unempfindlichen CD19 positiven B-Zell Erkrankungen.
2017-000120-10 Multicenter phase I trial of MB-CART20.1 for the treatment of patients with metastatic melanoma, Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen., Multizentrische Phase I Studie mit MB-CART20.1 zur Behandlung von Patienten mit metastasierenden Melanomen.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. Patient underwent treatment with a Miltenyi CAR T cell therapy at least 12 months prior to enrollment in long-term follow-up
  2. Patient has provided informed consent prior to enrollment

Exclusion criteria 1

  1. No exclusion criteria are defined for this long-term follow-up trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Percentage of patients with late-onset adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and adverse events of special interest (AESI) including relapse or progression of the underlying disease, life-threatening infections, death due to any cause, new and secondary malignancies

Secondary endpoints 5

  1. B- and T-lymphocyte count
  2. Height and weight, Tanner staging, menstruation status for pediatric patients
  3. Percentage of patients with detectable replication-competent lentivirus (RCL) (if results of 2 consecutive years are negative for an individual patient, further sampling will not be continued for this patient; if results of all samples in first year of primary trial were negative for an individual patient, sampling will not be continued for this patient in this long-term follow-up trial)
  4. Percentage of patients who relapse or progress since enrollment and rate of surviving patients
  5. Percentage of patients with detectable transgene levels (if results of 2 consecutive years are negative for an individual patient, further sampling will be stopped for this patient)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

MB-CART201

PRD8570562 · Product

Active substance
MB-CART201
Other product name
CD20 CAR transduced T cells
Pharmaceutical form
INFUSION
Route of administration
INTRAVENIOUS INFUSION
Authorisation status
Not Authorised
MA holder
MILTENYI BIOMEDICINE GMBH
Paediatric formulation
No
Orphan designation
No

MB-CART20191

PRD6952233 · Product

Active substance
Zamtocabtagene Autoleucel
Pharmaceutical form
INFUSION
Route of administration
INTRAVENIOUS INFUSION
Authorisation status
Not Authorised
MA holder
MILTENYI BIOMEDICINE GMBH
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/20/2327

MB-CART191

PRD8588266 · Product

Active substance
Autologous T-Cells Transduced with Lentiviral Vector Expressing a Chimeric Antigen Receptor Directed Against CD19
Substance synonyms
CD19-CAR_Lenti, MB-CART19.1
Other product name
CD19 CAR transduced T cells
Pharmaceutical form
INFUSION
Route of administration
INTRAVENIOUS INFUSION
Authorisation status
Not Authorised
MA holder
MILTENYI BIOMEDICINE GMBH
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Miltenyi Biomedicine GmbH

9 Total trials 6 Recruiting 2 Ended
Commercial
Sponsor organisation
Miltenyi Biomedicine GmbH
Address
Friedrich-Ebert-Strasse 68, Moitzfeld Moitzfeld
City
Bergisch Gladbach
Postcode
51429
Country
Germany

Scientific contact point

Organisation
Miltenyi Biomedicine GmbH
Contact name
Clinical Trial Desk

Public contact point

Organisation
Miltenyi Biomedicine GmbH
Contact name
Clinical Trial Desk

Third parties 5

OrganisationCity, countryDuties
Discovery Life Sciences Biomarker Services GmbH
ORG-100042520
 Kassel, Germany Laboratory analysis
International Drug Development Institute
ORG-100028563
 Ottignies-Louvain-La-Neuve, Belgium Code 10, Other
EvidentlQ Germany GmbH
ORG-100046039
 Munich, Germany E-data capture
SCRATCH Pharmacovigilance GmbH & Co. KG
ORG-100008874
 Butzbach, Germany Code 13
spm²-safety projects & more GmbH
ORG-100013935
 Hirschberg An Der Bergstrasse, Germany Code 8

Locations

1 EU/EEA country · 9 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Ongoing, recruiting 40 9
Rest of world — 0 —

Investigational sites

Germany

9 sites · Ongoing, recruiting
Universitaetsklinikum Erlangen AöR
Medizinische Klinik 5, Ulmenweg 18, Innenstadt, Erlangen
Universitaetsklinikum Muenster AöR
Medizinische Klinik A, KMT Zentrum, Albert-Schweitzer-Campus 1, Sentrup, Muenster
Universitaetsklinikum Wuerzburg AöR
Pediatric Hematology, Oncology and Stem Cell Transplantation, Josef-Schneider-Strasse 2, Grombuehl, Wuerzburg
University Hospital Cologne AöR
Klinik I für innere Medizin, Kerpener Strasse 62, Lindenthal, Cologne
Klinikum der Universitaet Muenchen AöR
Kinderonkologie, Lindwurmstrasse 4, Ludwigsvorstadt-Isarvorstadt, Munich
Universitaetsklinikum Tuebingen AöR
Med. Klinik, Innere Medizin II, Hämatologie, Onkologie, klinische Immunologie und Rheumatologie, Otfried-Mueller-Strasse 10, Nordstadt, Tuebingen
Charite Universitaetsmedizin Berlin KöR
Pädiatrische Klinik Schwerpunkt Onkologie und Hämatologie, Augustenburger Platz 1, Wedding, Berlin
Universitaetsmedizin Goettingen
Klinik für Hämatologie und Medizinische Onkologie, Bereich Stammzelltransplantation, Robert-Koch-Strasse 40, Weende, Goettingen
Westfaelische Wilhelms-Universitaet Muenster
Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Albert-Schweitzer-Campus 1, Sentrup, Muenster

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Germany 2024-05-05 2024-05-08

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2022-501648-14-00_redacted 4.0
Recruitment arrangements (for publication) K1_ Recruitment arrangements 3
Subject information and informed consent form (for publication) L1_SIS and ICF_12-15 years_German 3
Subject information and informed consent form (for publication) L1_SIS and ICF_16-17 years_German_redacted 3
Subject information and informed consent form (for publication) L1_SIS and ICF_6-11 years_German 2
Subject information and informed consent form (for publication) L1_SIS and ICF_adult_German_redacted 3
Subject information and informed consent form (for publication) L1_SIS and ICF_parent_German_redacted 3
Subject information and informed consent form (for publication) L1_SIS and ICF_pregnant partner_German_redacted 2
Subject information and informed consent form (for publication) L1_SIS and ICF_pregnant patient_German_redacted 2
Summary of Product Characteristics (SmPC) (for publication) G2_ SmPC MB-CART19_1 Not applicable 1
Summary of Product Characteristics (SmPC) (for publication) G2_ SmPC MB-CART20_1 Not applicable 1
Summary of Product Characteristics (SmPC) (for publication) G2_ SmPC_MB-CART2019_1 Not applicable 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_DE_2022-501648-14-00 4.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_ENG_2022-501648-14-00 4.0

Application history

4 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-08-31 Germany Acceptable
2023-11-14
 2023-11-17
2 SUBSTANTIAL MODIFICATION SM-1 2024-03-15 Germany Acceptable
2024-04-04
 2024-04-15
3 NON SUBSTANTIAL MODIFICATION NSM-1 2025-07-18 Germany Acceptable
2024-04-04
 2025-07-18
4 SUBSTANTIAL MODIFICATION SM-2 2025-12-18 Germany Acceptable
2026-02-05
 2026-02-19

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