Open-label Clinical Trial to Investigate the Safety and Tolerability of Allogeneic B-cell Concentrates for Immune Reconstitution After Allogeneic Stem Cell Transplantation Measured as Response to a Antedated Single Vaccination
B-cell therapy
Prospective, Open-label, Multicentre Clinical Trial, Phase I/IIa, to Investigate the Safety and Tolerability of Allogeneic B-cell Concentrates CD3+-Depleted, CD19+-Enriched, Cryopreserved (Single Administration After Day 120 Following Allogeneic Stem Cell Transplantation (SCT), Donor-identical) in 4 Groups With Escalating Doses for Immune Response Enhancement, Measured as Response to a Antedated Single Vaccination
1 other identifier
interventional
15
1 country
1
Brief Summary
The reconstitution of a functioning immune system after allogeneic stem cell transplantation takes months to years. Particularly memory B-lymphocytes reconstitute poorly with the current conditioning regimes. During the period of intense immune suppression the patients are extremely susceptible to bacterial, fungal and, most importantly, viral infections.The adoptive transfer of B-lymphocytes from the stem-cell donor might significantly enhance humoral immunity for the patient. Aim of the study is to evaluate a new cellular therapy with B-lymphocytes regarding safety. A booster vaccination after B-lymphocyte transfer will evaluate the functionality of the transferred B-lymphocytes in the patient.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2013
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2013
CompletedFirst Submitted
Initial submission to the registry
November 21, 2013
CompletedFirst Posted
Study publicly available on registry
December 11, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2015
CompletedMarch 26, 2014
March 1, 2014
2.1 years
November 21, 2013
March 24, 2014
Conditions
Outcome Measures
Primary Outcomes (3)
Number of participants with EBV DNA copies/ml plasma higher than 50,000
for 120 days after administration of study medication
Number of participants with signs of a post-transplant lymphoproliferative disorder (PTLD)
for 120 days after administration of study medication
Number of participants with adverse events (AEs), adverse reactions (ARs), serious adverse events (SAEs), serious adverse reactions (SARs) and suspected unexpected serious adverse reaction (SUSARs)
for 120 days after administration of study medication
Secondary Outcomes (5)
Change in the frequency of antibody-producing cells between dose groups
before and 7 days after preponed single vaccination
Change of mean absolute number of B-lymphocytes, naïve B-lymphocytes and memory B-lymphocytes between dose groups.
1 day before and up to 120 days after administration of study medication
Change of antigen-specific antibody concentration in serum/plasma between dose groups
1 day before and up to 120 days after administration of study medication
Change of Cytomegalovirus (CMV) DNA copies/ml plasma between dose groups
1 day before and up to 120 days after administration of study medication
Number of patients with >5,000 CMV DNA copies/ml plasma or with signs of organ infestation by CMV between dose groups.
up to 120 days after administration of study medication
Study Arms (1)
allogeneic donor derived B-lymphocytes
EXPERIMENTALInterventions
CD3+-depleted, CD19+-enriched, cryopreserved (single administration after day 120 following allogeneic stem cell transplantation, donor-identical) in 4 groups with escalating doses
Eligibility Criteria
You may qualify if:
- patients after allogeneic stem cell transplantation
- Serostatus for EBV: R-/D- oder R+/D- oder R+/D+
You may not qualify if:
- Serostatus for EBV: R-/D+
- Severe acute Graft versus Host Disease (GvHD) (Glucksberg grade III und IV)
- Chronic GvHD in middle- or high-risk group according to NIH staging
- Rituximab administration after SCT
- \>10.000 EBV DNA copies/ml plasma
- Recurrence of the haematological disorder needing therapeutic intervention
- Secondary transplantation
- SCT with transplant from a haploidentical donor
- SCT with transplant from umbilical cord blood
- CD34+-enriched transplant
- in vitro T-cell depleted transplant
- Pregnant or breast-feeding female
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Erlangen-Nürnberg Medical Schoollead
- University Hospital Regensburgcollaborator
- Wuerzburg University Hospitalcollaborator
- University Hospital, Essencollaborator
- German Research Foundationcollaborator
Study Sites (1)
Medical Department 5, University Hospital Erlangen
Erlangen, 91054, Germany
Related Publications (1)
Winkler J, Tittlbach H, Schneider A, Vasova I, Strobel J, Herold S, Maas S, Spriewald BM, Repp R, Kordelas L, Mach M, Wolff D, Edinger M, Mackensen A, Winkler TH. Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation. Blood Adv. 2024 May 28;8(10):2373-2383. doi: 10.1182/bloodadvances.2023012305.
PMID: 38467031DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Julia Winkler, MD
University Hospital Erlangen
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 21, 2013
First Posted
December 11, 2013
Study Start
November 1, 2013
Primary Completion
December 1, 2015
Study Completion
December 1, 2015
Last Updated
March 26, 2014
Record last verified: 2014-03