Expanded Natural Killer (NK) Cells for Multiple Myeloma Study
High-dose chemotherapy with melphalan and autologous hematopoietic stem cell transplantation (HSCT) is considered standard treatment for patients with multiple myeloma. While autologous HSCT may induce remission in patients resistant to standard chemotherapy, and has been shown to lead to long-lasting disease control in a subgroup of patients, the procedure is not curative. Given enough time and in the absence of a competing cause of death, all patients eventually relapse after auto-HSCT.
The only potentially curative approach currently available in the treatment of multiple myeloma (MM) is stem cell trans-plantation from an allogeneic donor. Allogeneic HSCT eradicates residual myeloma cells through T-cell mediated graft-versus-tumor effects. Allogeneic HSCT is, however, associated with significant risk of graft-versus-host disease and its use is therefore limited to younger patients with high risk dis-ease. Malignant plasma cells in multiple myeloma are also sensitive to natural killer cell lysis. Natural killer cells do not cause graft-versus-host disease, which has led to interest in their therapeutic use in patients with multiple myeloma.
We have previously shown that immunomagnetic separation of a highly pure NK cell product from a leukapheresis is possible and that these cells can be expanded up to 100-fold in a GMP-compatible setting. The current study aims to test the tolerability and feasibility of infusions of in vitro expanded haploidentical NK cells for patients after melphalan 200mg/m2 high dose chemotherapy and autologous HSCT in 10 patients. If feasible, the data will provide a basis for further prospective studies.
|Multiple Myeloma||Other: Treatment with in vitro expanded haploidentical NK cells||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Single Center Study to Assess Tolerability and Feasibility of Infusions of Allogeneic Expanded Haploidentical Natural Killer (NK) Cells in Patients Treated With High Dose Melphalan Chemotherapy and Autologous Stem Cell Transplantation for a Multiple Myeloma|
- Safety of expanded NK cell infusion [ Time Frame: One year after infusion. ]
- Treatment efficacy [ Time Frame: One year after treatment ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
Experimental: NK cell infusions
10 NK cell infusions day 3-30; Treatment with in vitro expanded haploidentical NK cells
Other: Treatment with in vitro expanded haploidentical NK cells
10 expanded NK-DLI will be applied at fixed intervals and to each patient within 30 days (3 applications per week, Mo/We/Fr) starting with increasing CD56+CD3- NK cell doses at 3 dose levels (1.5x10e6/kg, 1.5x10e7/kg and 1x10e8/kg) and, if safe, continuing with maximally 7 doses of 1x10e8/kg. Maximal cumulative T-cell dose is fixed at <1x10e5/kg
Please refer to this study by its ClinicalTrials.gov identifier: NCT01040026
|Contact: Jakob Passweg, MD, Prof.||41 61 265 firstname.lastname@example.org|
|Basel, BS, Switzerland, 4031|
|Contact: Jakob Passweg, MD, Prof. 41 61 265 2525 email@example.com|
|Principal Investigator: Jakob Passweg, MD, Prof.|
|Principal Investigator:||Jakob Passweg, MD, Prof.||Dep. of Hematology, Petersgraben 4, CH-4031 Basel|