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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Non Hodgkin's Lymphoma, Hodgkin's Disease, Myelodysplastic Syndrome, Multiple Myeloma, Aplastic Anemia

Intervention / Treatment
-----------------
* Biological: allogeneic donor derived B-lymphocytes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients after allogeneic stem cell transplantation Serostatus for EBV: R-/D- oder R+/D- oder R+/D+ Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: allogeneic donor derived B-lymphocytes<br> | Biological: allogeneic donor derived B-lymphocytes<br>* CD3+-depleted, CD19+-enriched, cryopreserved (single administration after day 120 following allogeneic stem cell transplantation, donor-identical) in 4 groups with escalating doses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |