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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia; Multiple Myeloma; Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Aplastic Anemia; Non Hodgkin's Lymphoma; Hodgkin's Disease
• Intervention / Treatment: Biological: allogeneic donor derived B-lymphocytes

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Julia Winkler, MD; Phone Number: +49 9131 85 43112; Email: julia.winkler@uk-erlangen.de
• Study Contact Backup: Name: Wolf Rösler, MD; Phone Number: +49 9131 85 43115; Email: wolf.roesler@uk-erlangen.de

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Recruiting
    • Medical Department 5, University Hospital Erlangen
    • Contact: Julia Winkler, MD; Phone Number: +49 9131 85 43112; Email: julia.winkler@uk-erlangen.de
    • Contact: Andreas Mackensen, MD; Phone Number: +49 9131 85 35954; Email: andreas.mackensen@uk-erlangen.de
    • Principal Investigator: Julia Winkler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients after allogeneic stem cell transplantation
2. Serostatus for EBV: R-/D- oder R+/D- oder R+/D+

Exclusion Criteria:

1. Serostatus for EBV: R-/D+
2. Severe acute Graft versus Host Disease (GvHD) (Glucksberg grade III und IV)
3. Chronic GvHD in middle- or high-risk group according to NIH staging
4. Rituximab administration after SCT
5. >10.000 EBV DNA copies/ml plasma
6. Recurrence of the haematological disorder needing therapeutic intervention
7. Secondary transplantation
8. SCT with transplant from a haploidentical donor
9. SCT with transplant from umbilical cord blood
10. CD34+-enriched transplant
11. in vitro T-cell depleted transplant
12. Pregnant or breast-feeding female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborators: German Research Foundation; University Hospital, Essen; Wuerzburg University Hospital; University Hospital Regensburg
• Investigators: Principal Investigator: Julia Winkler, MD, University Hospital Erlangen

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 11, 2013

Study Record Updates

• Last Update Posted (Estimate): March 26, 2014
• Last Update Submitted That Met QC Criteria: March 24, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Anemia; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Bone Marrow Failure Disorders; Lymphoma; Myelodysplastic Syndromes; Multiple Myeloma; Leukemia; Leukemia, Myeloid; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anemia, Aplastic
• Other Study ID Numbers: UKER-BLZ-PH1