Leukemia, Myeloid, Acute, Lymphoma, Myelodysplastic Syndromes, Neuroblastoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Rhabdomyosarcoma
Conditions
Brief summary
This is a phase I/II study of highly selected donor lymphocyte infusions in patients undergoing HLA-haploidentical hemopoietic stem cell transplantation. Patients will be offered pre-emptive NK-DLI early after HSCT. Three schedules of NK-cell infusion will be studied: Basel patients (adult and pediatric) will receive NK-DLI on days +40 and +100 (pre-emptive-late); Frankfurt patients (pediatric) will receive NK-DLI on days +3, +40, and +100 (pre-emptive early). Patients not receiving pre-emptive NK-DLI with loss in donor chimerism or with evidence of minimal residual disease will be offered therapeutic NK-DLI.
Interventions
BIOLOGICALCD3-depleted/CD56+ selected natural killer cells collected from apheresis products
NK DLI products containing \>1 10e7 NK cells/kg bodyweight (BW) and \< 1 x 10e5 T-cells/kg BW are administered at days +4 (Frankfurt only), and on days +40 and +100 (both centers)
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with acute/chronic leukemia, myelodysplastic syndrome, lymphoid neoplasia, solid tumor or bone marrow failure syndrome * signed informed consent of the patient (or his/her legal representative)
Exclusion criteria
* Patients with graft failure * Patients with any grade of active acute of chronic graft-versus-host disease (GvHD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of NK-DLI production | At day of transplant (day 0) | The feasibility of the production of expanded NK-cell DLI will be measured. Primary quality measures of the NK cell product are the number of NK cells that can be produced (CD56+/cluster of differentiation 3(CD3)- NK cell goal dose \>= 1 \* 10e7/kg body weight of recipient) as well as the degree of CD3 T-cell contamination (goal CD3+ T-cell dose \< 1 \* 10e5 / kg body weight of recipient). |
| Safety of NK DLI Infusion | Day +60 after transplant | The safety evaluation regards transfusion associated adverse events (fever, fall in blood pressure, transfusion site reactions, etc) and is evaluated at the time of NK DLI infusion. The primary long-term safety measure is the absence of acute graft-versus-host disease 30 days after the last NK DLI infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of NK DLI Infusions | 5 years after last NK DLI | The efficacy of NK DLI infusions will be assessed by evaluation of the rates of overall and disease free survival and the rate of disease relapse. As this is a single arm study, outcome measures assessed will be compared to those of historical controls treated with haploidentical HSCT without NK DLI infusions. |
Countries
Germany, Switzerland
Outcome results
None listed