Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
70
Countries
3
Sites
13
Large B-Cell Lymphoma (LBCL)
Efficacy: To assess clinical efficacy of ALLO-647 (in a lymphodepletion regimen before ALLO-501A) compared to FC alone as measured by PFS and assessed by IRC in subjects with R/R LBCL.
Key facts
- Sponsor
- Allogene Therapeutics Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20], Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 17 Oct 2023 → 29 Oct 2024
- Decision date (initial)
- 2023-08-28
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Allogene Therapeutics Inc.
External identifiers
- EU CT number
- 2023-503830-27-00
- ClinicalTrials.gov
- NCT05714345
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Efficacy, Therapy, Safety, Pharmacodynamic
Efficacy: To assess clinical efficacy of ALLO-647 (in a lymphodepletion regimen before ALLO-501A) compared to FC alone as measured by PFS and assessed by IRC in subjects with R/R LBCL.
Secondary objectives 11
- Efficacy: To assess the clinical efficacy of ALLO-647 as measured by ORR and assessed by IRC between treatment arms
- Efficacy: To assess clinical efficacy of ALLO-647 with FC (in a lymphodepletion regimen before ALLO-501A) compared to FC alone as measured by EFS and assessed by IRC in subjects with R/R LBCL.
- Efficacy: To characterize the efficacy of ALLO-647 as measured by DOR and assessed by IRC between treatment arms
- Efficacy: To characterize other aspects of the efficacy of ALLO-647, including PFS, response rate per investigator review, DOR, and overall survival
- Efficacy: To characterize the depth and duration of lymphodepletion with and without ALLO-647
- To characterize the PK of ALLO-647
- To characterize cellular kinetics of ALLO-501A when administered with and without ALLO-647
- To characterize the pharmacodynamics of ALLO-647 on host T cells
- To evaluate immunogenicity of ALLO-501A and of ALLO-647
- Safety: To evaluate the overall safety profile of ALLO-647 by comparing FCA lymphodepletion with FC lymphodepletion
- Safety: To evaluate the overall safety profile of ALLO-501A following lymphodepletion
Conditions and MedDRA coding
Large B-Cell Lymphoma (LBCL)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10012821 | Diffuse large B-cell lymphoma recurrent | 100000004864 |
| 21.0 | PT | 10012822 | Diffuse large B-cell lymphoma refractory | 100000004864 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | EXPAND This is a randomized, open-label, multicenter Phase 2 study evaluating lymphodepletion with fludarabine, cyclophosphamide, and ALLO-647 in comparison with fludarabine and cyclophosphamide alone in adult subjects with Relapsed/ Refractory LBCL.
Once eligibility has been established the treatment phase will occur over the span of approximately 1 week. During lymphodepletion, patients will receive fludarabine and cyclophosphamide with or without ALLO-647. ALLO-647 is an experimental antibody. One dose of ALLO-501A will be administered after the lymphodepletion period. ALLO-501A is made in the laboratory by modifying white blood cells, from a healthy person (donor) to help it recognize and fight LBCL.
Patients will be monitored for up to 5 years from the initial ALLO-501A infusion. After the 5 years patients will have the option to be followed for 10 additional years in a separate noninterventional, long-term, safety-monitoring study.
|
Randomised Controlled | None | FCA: Lymphodepletion with Fludarabine, Cyclophosphamide and ALLO-647 FC: Lymphodepletion with Fludarabine and Cyclophosphamide |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency, European Medicines Agency
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017
- Relapsed or refractory disease after at least 2 lines of chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Absence of significant donor (product)-specific anti-HLA antibodies (DSA) at screening.
- Adequate hematological function
- Adequate Renal Function
- Adequate Liver Function
Exclusion criteria 3
- Active central nervous system (CNS) involvement by malignancy
- Hypocellular bone marrow for age
- Autologous or allogeneic HSCT within last 6 months (24 weeks) prior to lymphodepletion.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Efficacy - PFS in FCA vs FC alone, defined as the time from randomization to disease progression, or relapse per the Lugano classification criteria (Cheson et al, 2014) as assessed by IRC or death
Secondary endpoints 19
- Efficacy - ORR in FCA vs FC alone, defined as assessment of CR or PR, assessed using the Lugano classification criteria 2014; Cheson , et al, 2014) by IRC at any time up through commencement of new anti-cancer therapy or withdrawal of consent.
- Efficacy - EFS in FCA vs FC alone, defined as the time from randomization to disease progression or relapse per the Lugano classification criteria 2014 as assessed by IRC and per investigator assessment, new anticancer therapy, or death
- Efficacy - DOR, defined as time from the first observed response to disease progression or relapse (per IRC and per investigator assessment) or death
- Efficacy - ORR in FCA vs FC alone per investigator assessment at any time up through commencement of new anti-cancer therapy or withdrawal of consent
- Efficacy - Best overall response (CR, PR, SD, PD) (per IRC and per investigator assessment) at any time up through commencement of new anti-cancer therapy or withdrawal of consent
- Efficacy - PFS in FCA vs FC alone, defined as time from the randomization to progression or relapse per investigator assessment per the Lugano classification criteria as assessed by investigator, or death
- Efficacy - TTR, defined as the time from randomization to the first observed response (per IRC and per investigator assessment)
- Efficacy - OS in FCA vs FC alone, defined as the time from randomization to death
- Efficacy - Depth and duration of lymphodepletion, as assessed by lymphocyte count
- PK concentrations will be used in a population PK model
- ALLO-501A expansion and persistence, eg, Cmax and AUC.
- Pharmacodynamics will be evaluated on host T cell counts
- The incidence of ADA against ALLO-501A scFv and/or TALEN®
- The incidence of ADA against ALLO-647
- Safety - AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647, and by FCA vs FC
- Safety - The incidence of infusion-related reactions, cytopenias, and infections
- Safety - AEs as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A and by FCA vs FC
- Safety - The incidence and severity of CRS, neurotoxicity, infections, hematologic toxicities, prolonged cytopenias, and GVHD
- Safety - The incidence and severity of clinically significant laboratory toxicities.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD10196712 · Product
- Active substance
- ALLO-501A
- Pharmaceutical form
- SUSPENSION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 120 million organisms million organisms
- Max total dose
- 120 million organisms million organisms
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- ATC code
- NOTASSIGN — -
- MA holder
- ALLOGENE THERAPEUTICS, INC.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10196741 · Product
- Active substance
- ALLO-647
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 90 mg milligram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Not Authorised
- ATC code
- NOTASSIGN — -
- MA holder
- ALLOGENE THERAPEUTICS, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Auxiliary 11
Fludarabin HEXAL® 25 mg/ml Konzentrat zur Herstellung einer Injektions- oder Infusionslösung
PRD766198 · Product
- Active substance
- Fludarabine Phosphate Ph. Eur.
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 30 mg/m2 milligram(s)/sq. meter
- Max total dose
- 90 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 74371.00.00
- MA holder
- HEXAL AG
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Solu-Cortef Powder for Solution for Injection or Infusion 100 mg
PRD1179840 · Product
- Active substance
- Hydrocortisone
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10 mg/Kg milligram(s)/kilogram
- Max total dose
- 30 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB09 — HYDROCORTISONE
- Marketing authorisation
- PA 0822/137/001
- MA holder
- PFIZER HEALTHCARE IRELAND
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cyclophosphamide 500 mg Powder for Solution for Injection or Infusion
PRD1649348 · Product
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 300 mg/m2 milligram(s)/square meter
- Max total dose
- 900 mg/m2 milligram(s)/square meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AA01 — CYCLOPHOSPHAMIDE
- Marketing authorisation
- PL 04416/1393
- MA holder
- SANDOZ LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD8915524 · Product
- Active substance
- Loratadine
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- R06AX13 — LORATADINE
- Marketing authorisation
- PA22871/008/001
- MA holder
- AZURE PHARMACEUTICALS LTD
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PREVYMIS 240 mg film-coated tablets
PRD5769611 · Product
- Active substance
- Letermovir
- Substance synonyms
- MK-8228, (S)-{8-fluoro-2-2[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)-phenyl]-3,4-dihydro-4-quinazolinyl} acetic acid, 2-[(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4H-quinazolin-4-yl]acetic acid
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 48000 mg milligram(s)
- Max treatment duration
- 100 Day(s)
- Authorisation status
- Authorised
- ATC code
- J05AX18 — -
- Marketing authorisation
- EU/1/17/1245/001
- MA holder
- MERCK SHARP & DOHME BV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabine phosphate 25 mg/ml Concentrate for Solution for Injection or Infusion
PRD1794909 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 30 mg/m2 milligram(s)/square meter
- Max total dose
- 90 mg/m2 milligram(s)/square meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- PL 20075/0379
- MA holder
- ACCORD HEALTHCARE LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PREVYMIS 480 mg film-coated tablets
PRD5769615 · Product
- Active substance
- Letermovir
- Substance synonyms
- MK-8228, (S)-{8-fluoro-2-2[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)-phenyl]-3,4-dihydro-4-quinazolinyl} acetic acid, 2-[(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4H-quinazolin-4-yl]acetic acid
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 48000 mg milligram(s)
- Max treatment duration
- 100 Day(s)
- Authorisation status
- Authorised
- ATC code
- J05AX18 — -
- Marketing authorisation
- EU/1/17/1245/002
- MA holder
- MERCK SHARP & DOHME BV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Quamatel 20 mg por és oldószer oldatos injekcióhoz
PRD870146 · Product
- Active substance
- Famotidine
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- A02BA03 — FAMOTIDINE
- Marketing authorisation
- OGYI-T-3848/06
- MA holder
- GEDEON RICHTER PLC.
- MA country
- Hungary
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Paracetamol 10 mg/ml solution for infusion
PRD9643730 · Product
- Active substance
- Paracetamol
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 650 mg milligram(s)
- Max total dose
- 1950 mg milligram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- N02BE01 — PARACETAMOL
- Marketing authorisation
- PA2299/056/001
- MA holder
- BAXTER HOLDING B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Phenergan 25mg/ml Solution for Injection
PRD431977 · Product
- Active substance
- Promethazine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 150 mg milligram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- R06AD02 — PROMETHAZINE
- Marketing authorisation
- PL 53886/0056
- MA holder
- OPELLA HEALTHCARE UK LIMITED, TRADING AS SANOFI
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
RoActemra 20 mg/mL concentrate for solution for infusion
PRD2154620 · Product
- Active substance
- Tocilizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 24 mg/kg milligram(s)/kilogram
- Max total dose
- 32 mg/kg milligram(s)/kilogram
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AC07 — -
- Marketing authorisation
- EU/1/08/492/001
- 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
Allogene Therapeutics Inc.
- Sponsor organisation
- Allogene Therapeutics Inc.
- Address
- 210 Grand Avenue
- City
- South San Francisco
- Postcode
- 94080-3707
- Country
- United States
Scientific contact point
- Organisation
- Allogene Therapeutics Inc.
- Contact name
- Clinical operations
Public contact point
- Organisation
- Allogene Therapeutics Inc.
- Contact name
- Clinical operations
Third parties 14
| Organisation | City, country | Duties |
|---|---|---|
| Adaptive Biotechnologies Corp. ORG-100044428
|
Seattle, United States | Other |
| Eurofins Viracor Biopharma Services Inc. ORG-100041736
|
Lenexa, United States | Other |
| Caprion Biosciences ORG-100039314
|
Charleroi, Belgium | Other |
| Neogenomics Laboratories Inc. ORG-100041804
|
Aliso Viejo, United States | Other |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Other |
| Labcorp Central Laboratory Services S.a.r.l. ORG-100011524
|
Meyrin, Switzerland | Other |
| Navigate Biopharma Services Inc. ORG-100032721
|
Carlsbad, United States | Other |
| Imperial Clinical Research Services International Limited ORG-100037442
|
Shepperton, United Kingdom | Other |
| Cellcarta Biosciences Inc. ORG-100042227
|
Montreal, Canada | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Laboratory Corporation Of America Holdings ORG-100041800
|
Burlington, United States | Other, Laboratory analysis |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 12, Code 13, Other, Code 2, Code 5, Data management, Code 8 |
| Fisher Bioservices Inc. ORG-100011655
|
Rockville, United States | Other |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Other |
Locations
3 EU/EEA countries · 13 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ended | 10 | 4 |
| Belgium | Ended | 10 | 5 |
| Germany | Ended | 15 | 4 |
| Rest of world
Australia, United States
|
— | 35 | — |
Investigational sites
Medical University Of Graz
Department of Internal Medicine, Neue Stiftingtalstrasse 6, 8010, Graz
Ordensklinikum Linz GmbH
Interne - Hämatologie und Onkologie, Fadingerstrasse 1, 4020, Linz
Medical University Of Vienna
Department for Internal Medicine I, Division of Hematology and Hemostaseology, Waehringer Guertel 18-20, Alsergrund, Vienna
SCRI CCCIT Ges.m.b.H.
Uniklikum Salzburg, Universitätsklinik für Innere Medizin III der PMU, Muellner Hauptstrasse 48, 5020, Salzburg
UZ Brussel
Hematology, Laarbeeklaan 101, 1090, Jette
Het Ziekenhuisnetwerk Antwerpen
Hematology, Lange Bremstraat 70, 2170, Antwerp
Cliniques Universitaires Saint-Luc
Hematology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
UZ Leuven
Hematology, Herestraat 49, 3000, Leuven
Het Ziekenhuisnetwerk Antwerpen
Hematology, Kempenstraat 100, 2030, Antwerp
University Hospital Jena KöR
Klinik für Innere Medizin II, Am Klinikum 1, Lobeda, Jena
Universitaetsklinikum Essen AöR
Klinik für Hämatologie und Stammzelltransplantation, Hufelandstrasse 55, Holsterhausen, Essen
Philipps University Marburg
Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie, Baldingerstrasse, 35043, Marburg
Universitaet Leipzig
Medical Department for Haematology, Cell Therapy and Hemostaseology, Liebigstrasse 22, Zentrum-Suedost, Leipzig
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2023-10-17 | ||||
| Belgium | 2023-11-07 | 2024-10-28 | 2023-12-04 | 2024-01-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| 2023-503830-27-00_Summary of Results SUM-102875
|
2025-10-20T23:33:23 | Submitted | Summary of Results |
| 2023-503830-27-00_ Summary of Results _FR SUM-102876
|
2025-10-20T23:33:13 | Submitted | Summary of Results |
| 2023-503830-27-00_ Summary of Results _NL SUM-102877
|
2025-10-20T23:33:06 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| 2023-503830-27-00_Lay person summary of results | 2025-10-20T23:34:37 | Submitted | Laypersons Summary of Results |
| 2023-503830-27-00_Lay person summary of results_FR | 2025-10-20T23:34:12 | Submitted | Laypersons Summary of Results |
| 2023-503830-27-00_Lay person summary of results_NL | 2025-10-20T23:33:38 | Submitted | Laypersons Summary of Results |
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | 2023-503830-27-00_Lay Person Summary of Results | 1 |
| Laypersons summary of results (for publication) | 2023-503830-27-00_Lay Person Summary of Results_FR | 1 |
| Laypersons summary of results (for publication) | 2023-503830-27-00_Lay Person Summary of Results_NL | 1 |
| Summary of results (for publication) | 2023-503830-27-00_ Summary of Results _FR | 1 |
| Summary of results (for publication) | 2023-503830-27-00_ Summary of Results _NL | 1 |
| Summary of results (for publication) | 2023-503830-27-00_Summary of Results | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-30 | Austria | Acceptable 2023-08-21
|
2023-08-23 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-10-19 | Austria | Acceptable 2024-01-22
|
2024-01-24 |