NK DLI in Patients After Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)

University Hospital, Basel, Switzerland15 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma Myelodysplastic Syndromes Lymphoma

Interventions

CD3-depleted/CD56+ selected natural killer cells collected from apheresis productsBIOLOGICAL

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)

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Feasibility of NK-DLI production

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).

Time frame: At day of transplant (day 0)

Safety of NK DLI Infusion

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.

Time frame: Day +60 after transplant

Secondary Outcomes

Efficacy of NK DLI Infusions

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.

Time frame: 5 years after last NK DLI