Daly 2-EU

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Miltenyi Biomedicine GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jul 2021 → ongoing

Decision date (initial)

2024-02-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Miltenyi Biomedicine GmbH, OMS Number: ORG-100022099

External identifiers

EU CT number

2023-506270-13-00

EudraCT number

2020-003908-14

ClinicalTrials.gov

NCT04844866

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Part I: The primary objective is to determine superiority of MB-CART2019.1 treatment compared to standard of care (SoC) therapy with R-GemOx (rituximab, gemcitabine and oxaliplatin) with respect to event-free survival in second-line therapy in participants with R-R DLBCL, who are non-eligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT).
Part II: The primary objective is to evaluate the efficacy of MB-CART2019.1 in younger, fit participants with R-R DLBCL.

Secondary objectives 7

1. Part I: To evaluate the efficacy of MB-CART2019.1 compared to SoC therapy.
2. Part I: To evaluate the safety and toxicity of MB-CART2019.1 compared to SoC therapy.
3. Part I: To evaluate changes in health-related quality of life (HRQoL) and lymphoma symptoms of participants receiving MB-CART2019.1 compared to SoC therapy. To evaluate the humoral immunogenicity against MB-CART2019.1. To evaluate changes in health-related quality of life (HRQoL) and lymphoma symptoms of participants receiving MB-CART2019.1 compared to SoC therapy.
4. Part I: To evaluate the humoral immunogenicity against MB-CART2019.1.
5. Part II: To evaluate the efficacy and safety of MB-CART2019.1
6. Part II: To evaluate changes in HRQoL of participants receiving MB-CART2019.1
7. Part II: To evaluate the humoral immunogenicity against MB-CART2019.1

Conditions and MedDRA coding

Relapsed/refractory diffuse large B cell lymphoma (R-R DLBCL)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003009-PIP01-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 27

1. 1. Part I: Histologically proven DLBCL and associated subtypes, according to the World Health Organization (WHO) 2016 classification
2. 10. Part I: Men with non-pregnant WOCBP partners must agree to use highly effective contraceptive measures
3. 11. Part I: In the opinion of the investigator, the participant must be able to comply with all study-related procedures, medication use and evaluations
4. 12. Part I: Mental capacity and legal ability to consent to participation in the clinical study.
5. 2. Part I: Relapsed or refractory disease after first-line chemoimmunotherapy
6. 3. Part I: Participants must have received adequate first-line therapy containing at least the combination of an anthracycline-based regimen and rituximab (anti-CD20 monoclonal antibody).
7. 4. Part I: Archival paraffin-embedded tumour tissue acquired ≤ 2 years (preferred: ≤ 2 months) prior to screening for the central pathology review to confirm DLBCL diagnosis must be made available for participation in this study. The lesion must be measurable (nodes > 1.5 cm in the long axis; extranodal lesions > 1 cm in the long axis) and positive on a positron emission tomography scan.
8. 5. Part I: Participants deemed ineligible to receive HDC followed by ASCT based on the treating physician’s assessment
9. 6. Part I: Age ≥ 18 years
10. 7. Part I: Measurable disease according to Lugano criteria. The lesion must be measurable (nodes > 1.5 cm in the long axis; extranodal lesions > 1 cm in the long axis) and positive on a positron emission tomography scan
11. 8. Part I: Estimated life expectancy of > 3 months for other reasons than the primary disease
12. 9. Part I: Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive measures
13. 1. Part II: Histologically proven DLBCL and associated subtypes, according to the WHO 2016 classification.
14. 2. Part II: Relapsed or refractory disease after first-line chemoimmunotherapy.
15. 3. Part II: Participant must have received adequate first-line therapy containing at least the combination of an anthracycline based regimen and rituximab (anti CD20 monoclonal antibody).
16. 4. Part II: Archival paraffin embedded tumour tissue acquired ≤ 2 years (preferred: ≤ 2 months) prior to screening for the central pathology review to confirm DLBCL diagnosis must be made available for participation in this study.
17. 5. Part II: Measurable disease according to Lugano criteria. The lesion must be measurable (nodes > 1.5 cm in the long axis; extranodal lesions > 1 cm in the long axis) and positive on a positron emission tomography scan.
18. 6. Part II: Approved treatment options not suitable according to investigator’s assessment.
19. 7. Part II: Age ≥ 18 and ≤ 70 years.
20. 8. Part II: Estimated life expectancy of > 3 months for other reasons than the primary disease.
21. 9. Part II: ECOG 0-1.
22. 10. Part II: Adequate bone marrow function, defined as: • Absolute neutrophil count ≥ 1,000/µL (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow biopsy). Platelet count ≥ 50,000/µL (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow biopsy). • Absolute lymphocyte count ≥ 100/µL.
23. 11. Part II: Adequate organ function, defined as: • New York Heart Association class < 2 or LVEF ≥ 50%. • No severe cardiac arrhythmias or QT prolongation (resting QTcF < 450 msec [male] or < 460 msec [female] at screening). • No clinically relevant pleural effusion or pericardial effusion. • Resting peripheral oxygen saturation ≥ 92% on room air. • Total bilirubin ≤ 2.0 × ULN, AST and/or ALT ≤ 5 × ULN. • Serum creatinine < 1.0 × ULN or eGFR (according to modified MDRD formula) ≥ 60 mL/min.
24. 12. Part II: WOCBP must agree to use highly effective contraceptive measures
25. 13. Men with non-pregnant WOCBP partners must agree to use highly effective contraceptive measures.
26. 14. Part II: In the opinion of the investigator, the participant must be able to comply with all study related procedures, medication use and evaluations.
27. 15. Part II: Mental capacity and legal ability to consent to participation in the clinical study.

Exclusion criteria 9

1. 1. Part I: Contraindications for R-GemOx, BR plus polatuzumab vedotin, cyclophosphamide and fludarabine as judged by the treating physician.
2. 2. Part I: Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
3. 3. Part I: Participants who have received more than one line of treatment for DLBCL or associated subtypes.
4. 4. Part I: Prior haematopoietic stem cell transplantation (HSCT; as first-line consolidation) < 3 months at the time of leukapheresis.
5. 5. Part I: ECOG performance status (PS) > 2
6. 1. Part II: Contraindications for cyclophosphamide and fludarabine as judged by the treating physician.
7. 2. Part II: Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
8. 3. Part II: Participants who have received more than one line of prior therapy for DLBCL or associated subtypes.
9. 4. Part II: Prior HSCT (as first-line consolidation) < 3 months at the time of leukapheresis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part I: Event-free survival (EFS), defined as the time between the date of randomisation and the date of objective disease progression, failure to achieve partial response (PR) or complete response (CR) at or beyond Week 8 after randomisation leading to a new anti-lymphoma therapy or death of any cause, whichever occurs first, based on independent review committee (IRC) assessment.
2. Part II: Best objective response rate (BORR), defined as the proportion of participants with at least one CR or PR between the date of MB-CART2019.1 infusion and the date of objective disease progression, the start of new antilymphoma therapy or the date of death from any cause, whichever occurs first, based on IRC assessment

Secondary endpoints 21

1. Part I: Progression-free survival (PFS), defined as the time between the date of randomisation and the date of objective disease progression or death of any cause, whichever occurs first, based on IRC assessment.
2. Part I: Best complete response rate (BCRR), defined as the proportion of participants with at least one CR assessment until Week 24 in the MB-CART2019.1 arm and Week 26 in the comparator arm based on IRC assessment.
3. Part I: Duration of complete response (DOCR), defined as the time between the date of a first CR and the date of assessment of objective disease progression or the date of death of any cause, whichever occurs first, based on IRC assessment.
4. Part I: Overall survival (OS), defined as time between the date of randomisation and the date of death of any cause.
5. Part II: DOR, defined as the time between the date of a first objective response (CR/PR) after MB-CART2019.1 infusion and the date of assessment of objective disease progression or the date of death of any cause, whichever occurs first, based on IRC assessment and based on investigator assessment.
6. Part II: PFS, defined as the time between the date of leukapheresis and the date of objective disease progression or death of any cause, whichever occurs first, based on IRC assessment and based on investigator assessment
7. Part II: PFS rates at 6 and at 12 months based on investigator assessment and based on IRC assessment.
8. Part II: OS, defined as time between the date of leukapheresis and the date of death of any cause.
9. Part II: BCRR, defined as the proportion of participants with CR between the date of MB-CART2019.1 infusion and the date of objective disease progression, the start of new anti-lymphoma therapy or the date of death from any cause, whichever occurs first based on IRC assessment and based on investigator assessment
10. Part II: DOCR, defined as the time between the date of a first CR and the date of assessment of objective disease progression or the date of death of any cause, whichever occurs first based on IRC assessment and based on investigator assessment
11. Part II: BORR based on investigator assessment.
12. Part II: Changes in HRQoL
13. Part II: Changes in lymphoma symptoms
14. Part II: Persistence of MB-CART2019.1 and phenotype of immune cell compositions based on flow cytometry analyses and real time quantitative polymerase chain reaction (qPCR).
15. Part II: Types and levels of cytokines (sIL-2R, IL-6, IL-10, IL-15, IFN-ʏ and TNFα).
16. Part II: Anti-MB-CART2019.1 antibody
17. Part II: Type, frequency and severity of AEs, SAEs, and AESIs.
18. Part II: Hospital days within 7 months after leukapheresis
19. Part II: ICU admission days within 7 months after leukapheresis.
20. Part II: Use of tocilizumab and/or high-dose steroids
21. Part II: Need for transfusions, prophylactic antimicrobial therapy, and gamma globulin substitution within 12 months after leukapheresis.

Investigational products

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

Test 1

Comparator 5

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Miltenyi Biomedicine GmbH

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 11

Locations

15 EU/EEA countries · 57 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Unexpected events 10 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 270 files

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

Application history

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