No registrations found.
ID
Source
Brief title
Health condition
Acute myeloid leukemia and Myelodysplastic syndrome with excess of blasts 2
Sponsors and support
Intervention
Outcome measures
Primary outcome
The study is divided in two phases.
The primary objective of phase I of the study is to evaluate the safety and toxicity of the infusion of ex vivo-expanded UCB-NK cells, both with and without SC IL-2, following a non-myeloablative immunosuppressive conditioning regimen in patients with AML or MDS with excess blasts-2 (EB-2).
The primary objective of phase IIa of the study is to evaluate the effect of UCB-NK cell adoptive immunotherapy in combination with SC IL-2 following a non-myeloablative immunosuppressive conditioning regime on disease activity in patients with AML/MDS-EB-2.
Secondary outcome
For both phases of the study secondary objectives include 1) evaluation of the in vivo lifespan and expansion potential of the donor NK cells following adoptive transfer, 2) exploration of the functional activity of the donor NK cells in peripheral blood (PB) and bone marrow (BM) and 3) evaluation of IL-2 serum levels and plasma cytokine concentrations pre- and post-administration of SC IL-2. An extra secondary objective for the phase IIa of the study is the number of patients bridged to transplant with this treatment protocol.
Background summary
In this study we will combine infusion of ex-vivo generated allogeneic natural killer cells with subcutaneous IL-2 to treat residual disease in AML or MDS-EB-2 patients. NK cells are generated from CD34+ hematopoietic stem and progenitor cells from umbilical cord blood (UCB-NK cells). A previous trial (PLMA25) has shown that administration of these cells is safe.
This study is divided in two phases. In phase I of the study we will evaluate the safety and toxicity of the NK-cell product in combination with IL-2, following a non-myeloablative immunosuppressive conditioning regimen. All patients will receive a fixed dose of 1.0-3.0 x 10^9 UCB-NK cells. The first 3 patients will receive no IL-2, the next 3 patients will receive IL-2 in a low dose and the next 6 patients IL-2 in a higher dose. IL-2 will be adminstered with a subcutaneous injection for 6 doses given every other day. After establishing the safety of UCB-NK cells combined with sc IL-2, we will continue with phase IIa of the study, evaluating the effect on disease activity of this treatment. We will use the highest tolerable IL-2 dose. Therefore another 11 patients will be included. The patients will be monitored for clinical toxicity, biological parameters in peripheral blood and bone marrow and disease activity.
Study objective
Natural killer cells are cells of the innate immunesystem and can kill tumor cells without prior sensitization. By infusing these cells hematologic cancer cells can be killed. IL-2 will activate the cells and prolong survival of the natural killer cells.
Study design
For phase 1 of the study dose-limiting toxicities (DLTs) have been defined for both UCB-NK cell or IL-2 toxicity. These will be evaluated at Day 28 after NK cell administration. The next cohort can start if all patients of the previous cohort reached day 28 after
NK cell infusion.
For phase 2 of the study the effect on disease activity will also be evaluated on day 28 after NK cell infusion, by performing bone marrow examination.
Intervention
Intravenous natural killer cell therapy with a preconditioning chemotherapy regimen with and without subcutaneous IL-2 administration.
Inclusion criteria
- Newly diagnosed AML or MDS EB-2 defined according to WHO 2016 criteria; AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related.
- Stable or at least non-rapidly progressive disease with or without disease controlling medication.
- Patients may belong to any of the following categories:
o Relapsed/refractory disease after treatment with intensive chemotherapy, hypomethylating agents, targeted agents, autologous or allo-SCT (at least 6 months ago) and DLI
o Newly diagnosed, untreated patients ineligible for allo-SCT
- Age ≥ 18 years
- WHO performance 0- 2 (Appendix 2)
- Life expectancy of > 4 months
- Written informed consent
- Hydrea is allowed as pre-treatment to control blast count until day -3
- Hypomethylating agents decitabine or azacitidine are allowed until day -7
Exclusion criteria
- Rapid-progressive disease in case of previous therapy (see Appendix 1).
- Patients on immunosuppressive drugs or active GvHD
- Patients with active infections (viral, bacterial or fungal); acute anti-infectious therapy must have been completed within 14 days prior to study treatment
- Severe cardiovascular disease (CTCAE III-IV)
- Severe pulmonary dysfunction (CTCAE III-IV)
- Severe renal dysfunction (CTCAE III-IV)
- Severe hepatic dysfunction (CTCAE III-IV)
- Severe neurological or psychiatric dysfunction (CTCAE III-IV)
- Presence of anti-HLA class I antibodies
- Patients on concurrent chemotherapy or interferon-alpha treatment
- Pregnancy or breastfeeding
Design
Recruitment
IPD sharing statement
Plan description
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9001 |
| CCMO | NL67150.000.19 |
| OMON | NL-OMON55708 |