Haploidentical Bone Marrow Stem Cell Transplantation in Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Natural Killer Cel Alloreactive Bone Marrow Transplantation for Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02519114
• Other study ID #: NL49476.000
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 28, 2015
• Last updated: February 9, 2017
• Start date: August 2015
• Est. completion date: June 2017

Study information

• Verified date: February 2017
• Source: Maastricht University Medical Center
• Contact: Janine Elssen van, MD PhD
• Phone: 31 43 3877026
• Email: janine.van.elssen[@]mumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Procedure:
• Donor Bone Marrow stem cell transplantation
KIR-mismatched haploidentical Bone Marrow stem cell transplantation

Locations

Country	Name	City	State
Netherlands	Maastricht university Medical center	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (scale)		1 year
Secondary	Response rate (scale)		analyzed at -7, 30, 60, 90, 120, 150, 180, 270 and 360 days post-transplatation
Secondary	Incidence of graft failure, engraftment and time to neutrophil and platelet recovery (hematology)		30 days after transplantation
Secondary	Incidence and Severity of Acute and Chronic GVHD (scale)		analyzed during follow-up of 1,5 years
Secondary	Non-Relapse Mortality (number)		1.5 years
Secondary	Evaluation of infections after haploBMT and T cell reconstitution (scale)		1 year after transplantation
Secondary	NK cell repertoire reconstitution and maturation rates including alloreactivity (facs)		1 year after transplantation
Secondary	NK cell repertoire in the Bone Marrow before and after transplantation (facs)		6 weeks after transplantation
Secondary	Cost calculation (euro)		1.5 years
Secondary	Quality of Life (questionnaire)		1.5 years