Clinical trial NCT01040026: Expanded Natural Killer (NK) Cells for Multiple Myeloma Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2009-12-25
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* \> 18 years, with multiple myeloma and indication for an autologous HSCT
* Available related haploidentical donor
* Written informed consent

Exclusion Criteria:

* Patients scheduled for autologous/allogeneic tandem HSCT

Primary outcomes:
measure: Safety of expanded NK cell infusion
timeFrame: One year after infusion.
Secondary outcomes:
measure: Treatment efficacy
timeFrame: One year after treatment
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital
state: BS
Study officials:
affiliation: Dep. of Hematology, Petersgraben 4, CH-4031 Basel
name: Jakob Passweg, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tschan-Plessl A, Kalberer CP, Wieboldt R, Stern M, Siegler U, Wodnar-Filipowicz A, Gerull S, Halter J, Heim D, Tichelli A, Tsakiris DA, Malmberg KJ, Passweg JR, Bottos A. Cellular immunotherapy with multiple infusions of in vitro-expanded haploidentical natural killer cells after autologous transplantation for patients with plasma cell myeloma. Cytotherapy. 2021 Apr;23(4):329-338. doi: 10.1016/j.jcyt.2020.09.009. Epub 2020 Nov 29.