Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
100
Countries
2
Sites
15
Large B-Cell Lymphoma (LBCL)
Phase 2 Primary Objectives: Efficacy To assess the clinical efficacy of ALLO-501A as measured by ORR 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] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 29 Sep 2023 → 12 Jan 2024
- Decision date (initial)
- 2023-07-11
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Allogene Therapeutics Inc.
External identifiers
- EU CT number
- 2022-501927-25-00
- ClinicalTrials.gov
- NCT04416984
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Therapy, Safety, Pharmacokinetic, Efficacy
Phase 2 Primary Objectives:
Efficacy To assess the clinical efficacy of ALLO-501A as measured by ORR and assessed by IRC in subjects with R/R LBCL.
Secondary objectives 10
- Secondary Objectives (Phase 1 and 2): Efficacy ALLO-501A: To characterize the efficacy of ALLO-501A as measured by DOR and assessed by IRC
- Secondary Objectives (Phase 1 and 2): Efficacy ALLO-501A: To characterize the efficacy of ALLO-501A as measured by DOR and assessed by investigator
- Secondary Objectives (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic ALLO-501A: To characterize cellular kinetics of ALLO-501A
- Secondary Objectives (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic ALLO-501A: To evaluate immunogenicity of ALLO-501A
- Secondary Objectives (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic ALLO-647: To characterize depth and duration of lymphodepletion
- Secondary Objectives (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic ALLO-647: To characterize the PK of ALLO-647
- Secondary Objectives (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic ALLO-647: To characterize the pharmacodynamics of ALLO-647
- Secondary Objectives (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic ALLO-647: To evaluate immunogenicity of ALLO-647.
- Secondary Objectives (Phase 1 and 2): Safety ALLO-501A: To evaluate the overall safety profile of ALLO-501A following lymphodepletion
- Secondary Objectives (Phase 1 and 2): Safety ALLO-647: To evaluate the overall safety profile of ALLO-647
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 |
| 21.1 | LLT | 10012857 | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory | 10029104 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Safety & Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With R/R LBCL This is a single-arm, open-label, multicenter Phase 1/2 study evaluating the safety, efficacy, cellular kinetics, and immunogenicity of ALLO-501A in adult subjects with R/R LBCL.
Once eligibility has been established the treatment phase will occur over the span of 6 days. During lymphodepletion, patients will receive fludarabine, cyclophosphamide, and 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.
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017.
- At least 1 measurable lesion at time of enrollment
- 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 8
- Active central nervous system (CNS) involvement by malignancy.
- Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy.
- Any other active malignancies that required systemic treatment within 3 years prior to enrollment.
- Radiation therapy within 2 weeks prior to ALLO-647.
- Prior irradiation to >25% of the bone marrow.
- Hypocellular bone marrow for age by institutional standard as determined from a bone marrow biopsy performed at time of screening.
- Autologous HSCT within last 6 months (24 weeks) or allogeneic HSCT within last 6 months (24 weeks) prior to ALLO-647.
- Subjects with active systemic bacterial, fungal, or viral infection requiring systemic treatment (including positive blood cultures within 7 days before starting lymphodepletion).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Phase 2 Primary Endpoints: Efficacy, ORR, defined as assessment of CR or PR, assessed using the Lugano classification criteria 2014; Cheson et al, 2014) by IRC.
Secondary endpoints 16
- Secondary Endpoints (Phase 1 and 2): Efficacy ALLO-501A: DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression per (Cheson et al, 2014) and per IRC (Phase 2 only) and per investigator assessment) or death, whichever comes first.
- Secondary Endpoints (Phase 1 and 2): Efficacy ALLO-501A: ORR per investigator assessment
- Secondary Endpoints (Phase 1 and 2): Efficacy ALLO-501A: Best overall response (CR, PR, SD, PD) (per IRC (Phase 2 only) and per investigator assessment)
- Secondary Endpoints (Phase 1 and 2): Efficacy ALLO-501A: PFS, defined as time from the enrollment date to progression, relapse, or death (per IRC (Phase 2 only) and per investigator assessment)
- Secondary Endpoints (Phase 1 and 2): Efficacy ALLO-501A: TTR, defined as the time from the enrollment date to the first observed response (per IRC (Phase 2 only) and per investigator assessment)
- Secondary Endpoints (Phase 1 and 2): Efficacy ALLO-501A: OS, defined as the time from the enrollment date to death
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: Depth of lymphodepletion, as assessed by lymphocyte count
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: Duration of lymphodepletion, as assessed by lymphocyte recovery
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: PK concentrations will be used in a population PK model
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: ALLO-501A expansion and persistence, eg, Cmax and AUC
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: Pharmacodynamics will be evaluated on host T cell counts.
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: The incidence of ADA against ALLO-501A scFv and/or TALEN®
- Secondary Endpoints (Phase 1 and 2): Pharmacokinetic and Pharmacodynamic for ALLO-501A and ALLO-647: Incidence of ADA against ALLO-647
- Secondary Endpoints (Phase 1 and 2): Safety ALLO-501A: AEs as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A, The incidence and severity of CRS, GVHD, infections, cytopenias, and neurotoxicity
- Secondary Endpoints (Phase 1 and 2): Safety ALLO-647 AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647, The incidence of infusion-related reactions, cytopenias, and infections
- Secondary Endpoints (Phase 1 and 2): Safety ALLO-647: The incidence and severity of clinically significant laboratory toxicities
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
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
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
Auxiliary 10
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 USE
- 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
Phenergan 25mg/ml Solution for Injection
PRD431977 · Product
- Active substance
- Promethazine Hydrochloride
- Substance synonyms
- PROMETHAZINE HCL
- 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
PRD8915524 · Product
- Active substance
- Loratadine
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- 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 USE
- 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
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
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
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
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
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 USE
- 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
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 13
| Organisation | City, country | Duties |
|---|---|---|
| Laboratory Corporation Of America Holdings ORG-100041800
|
Burlington, United States | Other, Laboratory analysis |
| Navigate Biopharma Services Inc. ORG-100032721
|
Carlsbad, United States | Other |
| Cellcarta ORG-100039881
|
Antwerp, Belgium | Other |
| 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 |
| Imperial Clinical Research Services International Limited ORG-100037442
|
Shepperton, United Kingdom | Other |
| Eurofins Viracor Biopharma Services Inc. ORG-100041736
|
Lenexa, United States | Other |
| Adaptive Biotechnologies Corp. ORG-100044428
|
Seattle, United States | Other |
| Labcorp Central Laboratory Services S.a.r.l. Meyrin ORG-100011524
|
Meyrin, Switzerland | Other |
| Neogenomics Laboratories Inc. ORG-100041804
|
Aliso Viejo, United States | Other |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Other |
| Labcorp Central Laboratory Services LP ORG-100044131
|
Indianapolis, United States | Other |
| Fisher Bioservices Inc. ORG-100011655
|
Rockville, United States | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
Locations
2 EU/EEA countries · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 15 | 7 |
| Spain | Ended | 20 | 8 |
| Rest of world
Australia, United States, Canada, United Kingdom
|
— | 65 | — |
Investigational sites
Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza Di Torino
Department of Molecular Biology and Health Science University of Torino, Corso Bramante 88, 10126, Turin
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Scienze Cliniche e Sperimentali Oncologia, Piazzale Spedali Civili 1, 25123, Brescia
Ospedale San Raffaele S.r.l.
Dipartimento di Oncologia e Onco-ematologia, Via Olgettina 60, 20132, Milan
Humanitas Research Hospital
Humanitas Cancer Center e Dipartimento di Oncologia ed Ematologia, Via Alessandro Manzoni 56, 20089, Rozzano
IRCCS Azienda Ospedaliero-Universitaria Di Bologna
UOC Ematologia, Via Pietro Albertoni 15, 40138, Bologna
Azienda Ospedaliera Papa Giovanni XXIII
Department of Oncology and Hematology, Piazza Oms 1, 24127, Bergamo
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOSD Malattie linfoproliferativ e extramidollari Dipartimento di Diagnostica per Immagini, Radiotera, Largo Francesco Vito 1, 00168, Rome
Hospital Universitario 12 De Octubre
Hematology, Bloque D, Avenida De Cordoba S/n, Madrid
Hospital Universitario De Salamanca
Hematology Service, Paseo De San Vicente 58-182, 37007, Salamanca
Hospital Universitario Donostia
Hematology Service and Hematopoietic Transplant Unit, Pasealeku Doct. Begiristain 109, 20014, Donostia
Hospital Universitario La Paz
Hematology Service, Paseo Castellana 261, 28046, Madrid
Hospital Universitari Vall D Hebron
Hematology Service, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Catalan Institute Of Oncology
Hematology Department, Avinguda Gran Via De L'hospitalet 199-203, 08908, L'hospitalet De Llobregat
Hospital General Universitario Gregorio Maranon
Hematology and hemotherapy service, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Clinico Universitario De Valencia
Hematology Department, Avenida Blasco Ibanez 17, 46010, Valencia
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 |
|---|---|---|---|---|---|
| Italy | 2023-10-20 | 2023-11-13 | |||
| Spain | 2023-09-29 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-02-07 | Italy | Acceptable 2023-07-11
|
2023-07-11 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-10-23 | Italy | Acceptable 2024-01-11
|
2024-01-12 |