HAPLOIDENTICAL BONE MARROW TRANSPLANTATION FROM NK ALLOREACTIVE DONORS FOR PATIENTS WITH HIGH RISK ACUTE MYELOID LEUKEMIA - A PHASE 2 STUDY

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 27

Inclusion Criteria

AML/RAEB patients < 76 years,
and
very poor risk based on at least one of the following criteria (modification of criteria in HOVON 132 study):
- no CR after first remission-induction course,
- MRD+ by WT1 testing after induction chemotherapy and no [t(8;21) or AML1-ETO and WBC <20], no inv16/t(16;16) or CBFB-MYH11, no CEBPA-biallelic mutation, or no FLT3ITD-/NPM1+.
- MRD+ by flowcytometry after 1st consolidative chemotherapy and no [t(8;21) or AML1-ETO and WBC <20], no inv16/t(16;16) or CBFB-MYH11, no CEBPA-biallelic mutation, or no FLT3ITD-/NPM1+.
- MK+,
- Abn 3q26,
- No CBF, EVI1+,
- No CBF, abn(17p) or p53 mutation,
- RUNX1 mutation or ASXL1 mutation
- Bi-allelic FLT3-ITD with FLT3-ITD/FLT3wt ratio of >0.6
- Relapsed AML
and
susceptible for NK-cell alloreactivity
and
the availability of a NK cell alloreactive haploidentical bone marrow donor
and
Written informed consent

Exclusion Criteria

- 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, see appendix ???);
- 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 year with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
- Breast-feeding female patients.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1-year progression-free survival from the start of chemotherapy treatment<br /><br>immediately prior to the bone marrow transplantation. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Best response on study<br /><br>- Engraftment after haploBMT (i.e. to what extent blood cells will be produced<br /><br>by donor bone marrow cells)<br /><br>- Incidence and severity of acute GVHD and chronic GVHD<br /><br>- (Serious) adverse events<br /><br>- Overall Survival (OS) from registration<br /><br>- Incidence and time to AML relapse<br /><br>- NRM at day +100 and at 1-year<br /><br>- Evaluation of infections during the first year after haploBMT<br /><br>- Quality of Life at 6 and 12 months after haploBMT<br /><br>- Costs of donor search, haploBMT itself and of follow-up and possible<br /><br>complications during the first year after haploBMT<br /><br>- NK cell repertoire recovery and maturation rate including the attainment of<br /><br>alloreactive potential<br /><br>- T and B cell recovery</p><br>