Expanded Natural Killer (NK) Cells for Multiple Myeloma Study

NCT ID: NCT01040026

Last Updated: 2023-04-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2020-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NK cell infusions

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

Group Type EXPERIMENTAL

Treatment with in vitro expanded haploidentical NK cells

Intervention Type OTHER

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

Interventions

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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

Intervention Type OTHER

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jakob Passweg, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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University Hospital

Basel, Canton of Basel-City, Switzerland

Site Status

Countries

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Switzerland

References

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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.

Reference Type DERIVED
PMID: 33268029 (View on PubMed)

Related Links

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Other Identifiers

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NK_MM_01

Identifier Type: -

Identifier Source: org_study_id

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