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

Multiple Myeloma Clinical Trial

— B-cell therapy  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02007811
• Other study ID #: UKER-BLZ-PH1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: November 21, 2013
• Last updated: March 24, 2014
• Start date: November 2013
• Est. completion date: December 2015

Study information

• Verified date: March 2014
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Julia Winkler, MD
• Phone: +49 9131 85 43112
• Email: julia.winkler[@]uk-erlangen.de
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Anemia, Aplastic
• Aplastic Anemia
• Chronic Myeloid Leukemia
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

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

Locations

Country	Name	City	State
Germany	Medical Department 5, University Hospital Erlangen	Erlangen

Sponsors (5)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School	German Research Foundation, University Hospital Regensburg, University Hospital, Essen, Wuerzburg University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with EBV DNA copies/ml plasma higher than 50,000		for 120 days after administration of study medication	Yes
Primary	Number of participants with signs of a post-transplant lymphoproliferative disorder (PTLD)		for 120 days after administration of study medication	Yes
Primary	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	Yes
Secondary	Change in the frequency of antibody-producing cells between dose groups		before and 7 days after preponed single vaccination	No
Secondary	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	No
Secondary	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	No
Secondary	Change of Cytomegalovirus (CMV) DNA copies/ml plasma between dose groups		1 day before and up to 120 days after administration of study medication	No
Secondary	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	No