Clinical trial NCT02519114: Haploidentical Bone Marrow Stem Cell Transplantation in Patients With Multiple Myeloma
Official title: Natural Killer Cel Alloreactive Bone Marrow Transplantation for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: M Myeloma
KIR ligand mismatch
Haploidentical
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2015-08-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this phase 2 study is to demonstrate that KIR-ligand mismatched haploBMT with post-transplant cyclophosphamide will improve progression free survival in poor risk multiple myeloma patients.

Detailed description: The goal of this study is to evaluate the effectiveness of a new treatment modality, the KIR-ligand mismatched haploidentical stem cell transplantation (haploBMT), for poor risk multiple myeloma (MM) patients. MM is a malignancy of plasma cells that usually resides in the bone marrow. Despite new treatment modalities that have been introduced in the last years, MM is still an incurable disease for most patients and median survival for the younger patients (\<65) is about 5 years. MM can be treated by several disease modifiers - classical chemotherapy, high dose chemotherapy and autologous stem cell transplantation (ASCT), immunomodulators like thalidomide and lenalidomide, and drugs like bortezomib that interact with relevant intracellular pathways of malignant plasma cells. Though these treatment modalities have improved overall survival and quality of life, patients are not cured.

Eligibility criteria: Inclusion Criteria:

* Patients with MM \<60 years.
* Poor prognosis MM patients, permissive for KIR-ligand mismatch and with a KIR-ligand mismatched haploidentical donor. Poor prognosis is based on:

  * Patients with early disease recurrence (within 12 months after first ASCT) or
  * Patients after a minimum of three lines of chemotherapy (including high dose therapy followed by ASCT rescue therapy) or
  * Poor risk based on the cytogenetic profile.
* Written informed consent
* No HLA identical related or 10/10 matched unrelated donor
* Permissive for KIR-ligand mismatch
* Responsive after reinduction therapy
* Measurable disease

Exclusion Criteria:

* - Patients with an full matched (10/10) donor, who will enroll in the HOVON 96 study
* Active uncontrolled infections
* Uncontrolled CNS involvement by the malignant disease
* Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)
* Severe pulmonary dysfunction (CTCAE grade III-IV)
* Severe neurological or psychiatric disease
* Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3 times upper limit of normal)
* Significant renal dysfunction (creatinine clearance \< 30 ml/min after rehydration)
* History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
* Any psychological, familial, lingual, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Breast-feeding female patients.
* Concurrent severe and/or uncontrolled medical condition (DM, hypertension, cancer).

Primary outcomes:
measure: Progression free survival (scale)
timeFrame: 1 year
Secondary outcomes:
measure: Response rate (scale)
timeFrame: analyzed at -7, 30, 60, 90, 120, 150, 180, 270 and 360 days post-transplatation
measure: Incidence of graft failure, engraftment and time to neutrophil and platelet recovery (hematology)
timeFrame: 30 days after transplantation
measure: Incidence and Severity of Acute and Chronic GVHD (scale)
timeFrame: analyzed during follow-up of 1,5 years
measure: Non-Relapse Mortality (number)
timeFrame: 1.5 years
measure: Evaluation of infections after haploBMT and T cell reconstitution (scale)
timeFrame: 1 year after transplantation
measure: NK cell repertoire reconstitution and maturation rates including alloreactivity (facs)
timeFrame: 1 year after transplantation
measure: NK cell repertoire in the Bone Marrow before and after transplantation (facs)
timeFrame: 6 weeks after transplantation
measure: Cost calculation (euro)
timeFrame: 1.5 years
measure: Quality of Life (questionnaire)
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht university Medical center
Study officials:
affiliation: Maastricht Medical University
name: Claudia Geesing
role: STUDY_DIRECTOR
References:
citation: Van Elssen C, van Gorkom G, Voorter C, von dem Borne P, Meijer E, Wieten L, Bos G. Haploidentical transplantation in patients with multiple myeloma making use of natural killer cell alloreactive donors. Ann Hematol. 2021 Jan;100(1):181-187. doi: 10.1007/s00277-020-04303-z. Epub 2020 Oct 28.