Multicentre, randomised study comparing autologous intravesical macrophage cell therapy (Bexidem®) to intravesical Bacillus Calmette-Guerin (BCG) therapy in patients with superficial papillary bladder cancer

ISRCTN ISRCTN35881130
DOI https://doi.org/10.1186/ISRCTN35881130
Secondary identifying numbers MAK-BLA-202
Submission date
16/04/2009
Registration date
27/05/2009
Last edited
11/06/2010
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Prof Maximilian Burger
Scientific

Oberarzt
Klinik für Urologie
Universität Regensburg
Landshuterstr. 65
Regensburg
93053
Germany

Study information

Study designPhase II/III multicentre open-label randomised study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titlePhase II/III, multicentre, open-label, randomised study comparing autologous intravesical macrophage cell therapy (Bexidem®) to intravesical Bacillus Calmette-Guerin (BCG) therapy in patients with superficial papillary bladder cancer who have undergone complete transurethral resection
Study acronymBexidem®
Study objectives1. Phase II step:
1.1. Primary objective: To demonstrate a superior safety profile of Bexidem® therapy with respect to 'frequent immunotherapy-linked adverse events' (FILAEs) compared to BCG therapy
1.2. Secondary objective: To evaluate overall efficacy and recurrence-free survival in patients treated with Bexidem® therapy

2. Phase III step:
2.1. Primary objective: To compare efficacy (recurrence-free survival) of Bexidem® therapy to BCG therapy
2.2. Secondary objective: To evaluate overall safety of Bexidem® therapy as compared to BCG therapy
Ethics approval(s)All participating centres received ethics approval prior to recruitment of the first participant:
1. Spain: Regional EC - CEIC Regional de la Comunidad de Madrid; Local EC - CEIC Autonomico de Ensayos Clinicos de Andalucia - Consejeria de Salud; Local EC - Comité Etico de Investigacion Clinica de Galicia SERGAS
2. Hungary: Central EC Central Ethics Committee - Egészségügyi és Tudományos Tanács; Institutional Research Ethic Committee - Fövàrosi Szent Istvàn Hospital; Institutional Research Ethic Committee - Budai Irgal Masrendi Intézményi Kutatàsetikai Bizottsàg; IKEB Hatarozat dön tésröl; Regionalis Kuratasetukai Bizottsaga (Györ - Moson - Sopron etc..) - Egészségügyi és Tudományos Tanács; Local Ethic Committee Bajcsy - Zsilinszky Hospital; Regional and Institutional Committee of Science and research Ethics - Semmelweis Hospital; Local Ethic Committee Jahn Ferenc South-Pest Hospital; Regionalis Kuratasetukai Bizottsaga (Györ - Moson - Sopron etc..) - Egészségügyi és Tudományos Tanács; Institutional Research Ethic Committee of lcal Government of Capital City; Local Ethic Committee Bàcs - Kiskun County Hospital
3. France: Central EC - CCPPRB du l'Hopital Paris
4. Germany: Ethik-Kommission Medizinische - Fakultät Universität Regensburg; Ethikkommission Med. Fakultät der HHU Düsseldorf; Ethikkommission Charité - Universitätsmedizin; Ethikkommission - Medizinischen Fakultät der Technischen Universität; Ethikkommission der Landesärztekammer Rheinland-Pfalz
5. Belgium: Commission d'Ethique Biomédicale - Hospitalo-Facultaire; Comité Éthique - CHR de la Citadelle; Etisch Comité O.L. Vrouwziekenhuis; Etisch Comité AZ Groeninge
6. Luxembourg: Comité Éthique CNER 18
Health condition(s) or problem(s) studiedSuperficial papillary bladder cancer
InterventionDosage and administration:
Three treatment cycles: first cycle consists of either 6 weekly Bexidem® instillations (0.5 - 2 x 10^8 cells in a total volume of 50 ml per instillation) or BCG instillations (1 - 19.2 x 10^8 CFU in a total volume of 50 ml). Maintenance consists of two cycles (at month 3 and month 6) of each three weekly Bexidem® instillations, or 3 weekly BCG instillations.

Study duration:
Phase II: Individual patient participation: 24 months including follow-up observation. Total study duration: 42 months
Phase III: Individual patient participation: 24 months including follow-up observation. Total study duration: dependent upon total number of patients
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II/III
Drug / device / biological / vaccine name(s)Bexidem®
Primary outcome measurePhase II: To demonstrate a superior safety profile of Bexidem® with respect to FILAEs compared to BCG therapy.
Phase III: To compare efficacy (recurrence-free survival) of Bexidem® therapy to BCG therapy.

The comparison of toxicity will be performed after all patients in the Phase II step have completed all cycles of treatment and at least three months of follow up (month 9). The recurrence-free survival in each group will be estimated after all Phase II patients have completed at least six months of follow up after the last treatment (month 12 visit). These analyses will serve as the basis for a decision to proceed to the Phase III step as well as to estimate the expected recurrence-free survival in the two groups and recalculate the sample size required for the Phase III step.
Secondary outcome measuresPhase II: To evaluate overall efficacy and recurrence-free survival in patients treated with Bexidem® therapy.
Phase III: To evaluate overall safety of Bexidem® therapy as compared to BCG.

The comparison of toxicity will be performed after all patients in the Phase II step have completed all cycles of treatment and at least three months of follow up (month 9). The recurrence-free survival in each group will be estimated after all Phase II patients have completed at least six months of follow up after the last treatment (month 12 visit). These analyses will serve as the basis for a decision to proceed to the Phase III step as well as to estimate the expected recurrence-free survival in the two groups and recalculate the sample size required for the Phase III step.
Overall study start date25/06/2004
Completion date16/03/2007

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPhase II: 138 patients (69 per arm); up to 512 additional patients for phase III
Key inclusion criteria1. Male and female patients
2. At least 18 years of age
3. Fully resected papillary transitional cell carcinoma
4. Stage TaGI, TaGII, TaGIII, T1GI or T1GII (N0, M0)
5. Either of the following:
5.1. Plurifocal tumours
5.2. Unifocal tumour provided greater than or equal to two tumour occurrences within the last 24 months
6. World Health Organization (WHO) performance status 0 - 2
7. Normal upper urinary tract as documented by intravenous (IV) urography or computed tomography (CT) scan
8. Blood creatinine less than 200 umol/L
9. Alanine aminotransferase (ALT) and aspartate aminotrasferase (AST) less than 2.5 x upper limit of normal (ULN)
10. Leukocytes greater than or equal to 3,500/mm^3
11. Able to understand and follow treatment scheme
12. Signed and dated Informed Consent
Key exclusion criteria1. Greater than or equal to T1GIII bladder cancer
2. Carcinoma in situ (CIS)
3. Active tuberculosis
4. Other active infection (including urinary tract infection) and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B or hepatitis C infection
5. History of other active malignancy within five years, except adequately treated basal cell and squamous cell carcinoma of the skin
6. Other serious illness or medical conditions (e.g. history of significant cardiac or respiratory dysfunction)
7. Patients with a contra-indication preventing apheresis
8. History of autoimmune-related disorder
9. Known hypersensitivity to any of the components of the study drugs (e.g. dimethylsulphoxide [DMSO])
10. Immunosuppression or congenital or acquired immune deficiencies, whether due to concurrent disease (e.g. acquired immune deficiency syndrome [AIDS], leukaemia, lymphoma), cancer therapy (cytotoxic drugs, radiotherapy) or immunosuppressive therapy (e.g. corticosteroids, cyclosporin)
11. Family history of Creutzfeldt-Jacob disease and/or risk of Creutzfeldt-Jacob disease defined as patient having received extracted growth hormone or neurosurgery before 1996
12. Prior systemic reaction to BCG therapy
13. Pregnant or nursing women
Date of first enrolment25/06/2004
Date of final enrolment16/03/2007

Locations

Countries of recruitment

  • Belgium
  • France
  • Germany
  • Hungary
  • Luxembourg
  • Spain

Study participating centre

Oberarzt
Regensburg
93053
Germany

Sponsor information

IDM Pharma SA (France)
Industry

172 rue de Charonne
Paris Cedex 11
75545
France

http://www.idm-pharma.com
ROR logo https://ror.org/048p4wq89

Funders

Funder type

Industry

IDM Pharma SA (France)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 08/06/2010 Yes No
BMC - Part of Springer Nature Springer Nature