Long-term follow-up of patients previously treated with autologous T cells genetically modified with viral vectors.

2024-511684-28-00 Protocol AUTO-LT1 Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 1 Sep 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 4 sites · Protocol AUTO-LT1

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 111
Countries 1
Sites 4

Potential malignancy in patients who received treatment with Autolus CAR T cell therapy.

Long-term safety

Key facts

Sponsor
Autolus Limited
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Immune System Diseases [C20], Diseases [C] - Neoplasms [C04]
Trial duration
1 Sep 2025 → ongoing
Decision date (initial)
2024-07-19
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Autolus Limited

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Long-term safety

Secondary objectives 6

  1. Survival
  2. B-cell/T-cell aplasia
  3. Clinical efficacy of AUTO CAR T cell therapy in patients enrolled prior to disease progression
  4. Chimeric antigen receptor (CAR) transgene persistence
  5. Replication competent retrovirus (RCR) or lentivirus (RCL) emergence
  6. Insertional mutagenesis

Conditions and MedDRA coding

Potential malignancy in patients who received treatment with Autolus CAR T cell therapy.

VersionLevelCodeTermSystem organ class
21.0 LLT 10000845 Acute lymphoblastic leukemia 10029104
22.0 PT 10029547 Non-Hodgkin's lymphoma 100000004864
21.1 PT 10042945 Systemic lupus erythematosus 100000004859

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 AUTO-LT1
Patients may be enrolled following their AUTO CAR T cell therapy treatment and will be followed for up to 15 years (or death, whichever happens first) after the first AUTO CAR T cell therapy infusion. Patients will be monitored for safety, as described in the primary outcome measures, every 3 months for the year following the first AUTO CAR T cell therapy infusion, then every 6 months for the next 4 years and then annually for the following 10 years.
 Not Applicable None

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2019-001937-16 An Open-Label, Multi-Centre, Phase Ib/II Study Evaluating The Safety and Efficacy Of AUTO1, A CAR T Cell Treatment Targeting CD19, In Adult Patients With Relapsed Or Refractory B Cell Acute Lymphoblastic Leukaemia., Estudio en fase Ib/II, multicéntrico y sin enmascaramiento para evaluar la seguridad y eficacia de AUTO1, un tratamiento con linfocitos T CAR dirigido a CD19, en pacientes adultos con leucemia linfoblástica aguda de linfocitos B recidivante o refractaria
2023-508236-60-00 A Single-Arm, Open-Label, Phase 1 Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients with Severe, Refractory Systemic Lupus Erythematosus Autolus Limited
2023-506307-26-00 A Single-Arm, Open-Label, Multi-Centre, Phase Ib Study Evaluating the Safety and Preliminary Efficacy of AUTO1 in Pediatric Patients with CD19-Positive Relapsed/ Refractory (r/r) B cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B cell Non-Hodgkin Lymphoma (B NHL) Autolus Limited
2017-001965-26 A SINGLE ARM, OPEN-LABEL, MULTI-CENTRE, PHASE I/II STUDY EVALUATING THE SAFETY AND CLINICAL ACTIVITY OF AUTO4, A CAR T CELL TREATMENT TARGETING TRBC1, IN PATIENTS WITH RELAPSED OR REFRACTORY TRBC1 POSITIVE SELECTED T CELL NON-HODGKIN LYMPHOMA, Étude de phase I/II, multicentrique, en ouvert, à un seul bras, visant à évaluer la sécurité et l’activité clinique d’AUTO4, un traitement par cellules CAR-T ciblant TRBC1, chez des patients atteints de lymphomes non hodgkiniens à cellules T positives à TRBC1 réfractaires ou en rechute., ESTUDIO DE FASE I/II, MULTICÉNTRICO, ABIERTO Y DE UN SOLO GRUPO PARA EVALUAR LA SEGURIDAD Y LA ACTIVIDAD CLÍNICA DE AUTO4, UN TRATAMIENTO DE LINFOCITOS T-CAR DIRIGIDO A TRBC1, EN PACIENTES CON LINFOMA NO HODGKIN DE LINFOCITOS T SELECCIONADO TRBC1 POSITIVO RECIDIVANTE O REFRACTARIO

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. Patients must have received an AUTO CAR T cell therapy on a previous treatment study.
  2. Patients must have provided informed consent for long-term follow-up study prior to participation.
  3. Patients must be able to comply with the study requirements.

Exclusion criteria 1

  1. There are no exclusion criteria for this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

  1. Incidence of serious adverse events related to AUTO CAR T cell therapy
  2. New malignancies
  3. Other designated adverse events of special interest related to AUTO CAR T cell therapy

Secondary endpoints 6

  1. Overall survival for up to 15 years after the first AUTO CAR T cell therapy infusion
  2. Duration of supportive care
  3. Duration of response, progression-free survival
  4. Proportion of patients with detectable vector copy number in peripheral blood for up to 15 years from first AUTO CAR T cell therapy infusion
  5. Confirm / monitor for absence of detectable RCR/RCL for up to 15 years from first AUTO CAR T cell therapy infusion
  6. In case of new malignancy: Insertion site analysis to determine insertional mutagenesis as potential cause/contributor

Investigational products

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

Test 2

AUTO1

PRD8852218 · Product

Active substance
Autologous Enriched T Cells Retrovirally Transduced to Express Two Chimeric Antigen Receptors Targeting CD19 and CD22
Pharmaceutical form
INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
100 U/g unit(s)/gram
Max total dose
100 U/g unit(s)/gram
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
AUTOLUS LIMITED
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/22/2605

AUTO4

PRD4966877 · Product

Active substance
AUTO4
Pharmaceutical form
INTRAVENOUS INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
25 U/g unit(s)/gram
Max total dose
25 U/g unit(s)/gram
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
AUTOLUS LIMITED
Paediatric formulation
No
Orphan designation
No

Auxiliary 2

MabThera 100 mg concentrate for solution for infusion

PRD2159285 · Product

Active substance
Rituximab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
375 mg/m2 milligram(s)/sq. meter
Max total dose
375 mg/m2 milligram(s)/sq. meter
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
L01XC02 — RITUXIMAB
Marketing authorisation
EU/1/98/067/001
MA holder
ROCHE REGISTRATION GMBH
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

MabThera 500 mg concentrate for solution for infusion

PRD2154043 · Product

Active substance
Rituximab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
375 mg/m2 milligram(s)/sq. meter
Max total dose
375 mg/m2 milligram(s)/sq. meter
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
L01XC02 — RITUXIMAB
Marketing authorisation
EU/1/98/067/002
MA holder
ROCHE REGISTRATION GMBH
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Autolus Limited

6 Total trials 4 Recruiting 1 Ended
Commercial
Sponsor organisation
Autolus Limited
Address
191 Wood Lane
City
London
Postcode
W12 7FP
Country
United Kingdom

Scientific contact point

Organisation
Autolus Limited
Contact name
Ram Malladi

Public contact point

Organisation
Autolus Limited
Contact name
Ram Malladi

Locations

1 EU/EEA country · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ongoing, recruiting 21 4
Rest of world
United States, United Kingdom
 — 90 —

Investigational sites

Spain

4 sites · Ongoing, recruiting
Hospital Universitari Vall D Hebron
Paediatric Haemato-Oncology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital Universitario Y Politecnico La Fe
Hematology, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital Infantil Universitario Nino Jesus
Paediatric Haemato-Oncology, Avenida Menendez Pelayo 65, 28009, Madrid
Hospital Universitari Vall d'Hebron
Haematology, Passeig de la Vall d'Hebron 119, Spain, Barcelona

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2025-09-01 2025-09-01

Results and documents

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

Documents 20 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol modification nr 4_2024-511684-28-00_Redacted 4.0
Protocol (for publication) D1_Protocol_2024-511684-28-00_Not for publication n/a
Recruitment arrangements (for publication) R2_ Recruitment and Informed consent procedure_14Jun2024 NA
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO LT1 12 to17yrs_V1_11Jun24 1
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO LT1 8 to11yrs_V1_11Jun24 1.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO LT1 Child Assent Form_V1_11Jun24 1
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO LT1 Patient Becoming Pregnant ICF_V2_09Jul2024 V2.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO LT1 Pregnant Partner ICF_V2_09Jul2024 V2.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO-LT1_Parent Guardian ICF_V3_29Jul2024_clean 3.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO-LT1_Parent Guardian ICF_V3_29Jul2024_tracked 3.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO-LT1_Patient Becoming Pregnant ICF_V2_09Jul24_tracked 2
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO-LT1_Pregnant Partner ICF_V2_09Jul24_tracked 2
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO-LT1_Standard ICF_V3_29Jul2024_clean 3.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_AUTO-LT1_Standard ICF_V3_29Jul2024_tracked 3.0
Subject information and informed consent form (for publication) L2_ Other subject information material_AUTO LT1 Adolescent to Adult Re-consent Letter_V1_11Jun24 1
Subject information and informed consent form (for publication) L2_ Other subject information material_AUTO-LT1_GP Letter_V2_29Jul2024_clean 2.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EN_2024-511684-28-00_Not for publication 3
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EN_2024-511684-28-00_Redacted 4.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_ES_2024-511684-28-00_Not for publication 3
Synopsis of the protocol (for publication) D1_Protocol Synopsis_ES_2024-511684-28-00_Redacted 4.0

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-03-13 Spain Acceptable
2024-05-23
 2024-07-19
2 SUBSTANTIAL MODIFICATION SM-1 2024-08-02 Spain Acceptable
2024-10-07
 2024-10-14
3 NON SUBSTANTIAL MODIFICATION NSM-1 2025-06-26 Spain Acceptable
2024-10-07
 2025-06-26
4 NON SUBSTANTIAL MODIFICATION NSM-2 2026-03-18 Spain Acceptable
2024-10-07
 2026-03-18