NCT01040026

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1 multiple-myeloma

Timeline
Completed

Started Oct 2012

Longer than P75 for phase_1 multiple-myeloma

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 23, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 25, 2009

Completed
2.8 years until next milestone

Study Start

First participant enrolled

October 1, 2012

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
4.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2020

Completed
Last Updated

April 4, 2023

Status Verified

April 1, 2023

Enrollment Period

3.9 years

First QC Date

December 23, 2009

Last Update Submit

April 3, 2023

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

  • Safety of expanded NK cell infusion

    One year after infusion.

Secondary Outcomes (1)

  • Treatment efficacy

    One year after treatment

Study Arms (1)

NK cell infusions

EXPERIMENTAL

10 NK cell infusions day 3-30; Treatment with in vitro expanded haploidentical NK cells

Other: Treatment with in vitro expanded haploidentical NK cells

Interventions

Treatment with in vitro expanded haploidentical NK cellsOTHER

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

NK cell infusions

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Patients scheduled for autologous/allogeneic tandem HSCT

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (1)

  • 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.

    PMID: 33268029DERIVED

Related Links

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Jakob Passweg, MD, Prof.

    Dep. of Hematology, Petersgraben 4, CH-4031 Basel

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 23, 2009

First Posted

December 25, 2009

Study Start

October 1, 2012

Primary Completion

September 1, 2016

Study Completion

November 1, 2020

Last Updated

April 4, 2023

Record last verified: 2023-04

Locations

CH(1)