The aim of the study is demonstrating that progression free survival will improve after KIR-mismatched haploidentical bone marrow transplantation.
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival 18 weeks after transplantation.
Secondary outcome
1. Response rate
2. Incidence of graft failure, engraftment and time to neutrophil and platelet
recovery
3. Incidence and Severity of Acute and Chronic GVHD
4. Non-Relapse Mortality
5. Evaluation of infections after haploBMT and T cell reconstitution
6. NK cell repertoire reconstitution and maturation rates including
alloreactivity
7. NK cell repertoire in the Bone Marrow before and after (6 weeks)
transplantation
8. Cost calculation
9. Quality of Life
Background summary
Eventually almost all multiple myeloma patients will succumb to the disease.
Mainly for patients with an early recurrence after standard therapy further
treatment options are limited. Therefore, new treatment options are necessary.
An option is a bone marrow transplantation with donors selected on NK cell
alloreactivity. In the laboratory and in mouse models, our group and others
have shown that this alloreactivity results in antitumor responses. For NK cell
alloreactivity an haploidentical stemcel transplantation is used in this
study. This form of transplantation is being utilized for leukemia in many
centers all over the world (also in Maastricht). For multiple myeloma there is
not yet a study published demonstrating the effect of haploidentical
transplantation focusing on NK cell alloreactivity.
Study objective
The aim of the study is demonstrating that progression free survival will
improve after KIR-mismatched haploidentical bone marrow transplantation.
Study design
Fase II study in which a maximum of 24 patients will be treated by
haploindetical bone marrow transplantation with NK cell alloreactivity. Primary
objective is progression free survival after 18 months.
Intervention
Donor KIR-ligand mismatched haploidentical bone marow transplantation.
Study burden and risks
We expect that a substantial number of subjects will develop severe
complications (infections, graft versus host disease or organ failure) due to
treatment, even though the treatment protocol is focused on prevention of these
complications. Treatment related mortality is expected to occur.
The subject will be admitted for a few weeks after which intensive follow-up in
the out-patient department will follow. Readmissions are likely to occur.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
- Patients with MM <66 years.
- Poor prognosis MM patients, permissive for KIR-ligand mismatch and with a KIR-ligand mismatched haploidentical donor. Poor prognosis is based on:
o Patients with early disease recurrence (within 12 months after first ASCT) or
o Patients after a minimum of three lines of chemotherapy (including high dose therapy followed by ASCT rescue therapy) or
o Poor risk based on the cytogenetic profile.
- Written informed consent
- If there is no HLA identical related or 10/10 matched unrelated donor
- Permissive for KIR-ligand mismatch
- At least partial response after reinduction therapy
- Measurable disease
Exclusion criteria
- Active uncontrolled infections
- Patients that are known to be HIV positive.
- Patients with Donor specific HLA-antibodies
- 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 cell 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).
- Pregnant female patient. During the study pregnancy must be prevented by the use of contraceptives.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49476.000.14 |