A Phase I Trial of Donor Enriched Activated NK (DEA-NK) Cell Infusion Post Haploidentical Stem Cell Transplant for Refractory Myeloid Malignancies
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|ClinicalTrials.gov Identifier: NCT05375253|
Recruitment Status : Not yet recruiting
First Posted : May 16, 2022
Last Update Posted : May 16, 2022
Patients with relapse refractory myeloid malignancies [acute myeloid leukemia (AML) myelodysplastic(MDS)/myeloproliferative(MPD) disorders] have no therapeutic options for long term remission. Haploidentical cytokine activated (IL-12, IL-18, IL-15) natural killer (NK) cell immunotherapy has been used with some success in treating patients with refractory relapsed AML. One limiting factor to the in-vivo expansion of infused activated NK cells is the recovery of recipient's immune system rejecting the infused NK cells. The use of haploidentical activated NK cell therapy post haploidentical transplant is an attractive option to induce in-vivo persistence of the infused NK cells and support anti leukemic efficacy.
This is a pilot phase Ib trial testing the feasibility, safety and immunologic effects of dose escalated donor enriched (αβ-TCR+/CD19+ double depleted mononuclear cells) activated natural killer cell infusion (DEA-NK) on day +7 post haploidentical stem cell transplantation (Haplo-Tx) with post-transplant cyclophosphamide (PTCY). Inclusion criteria include: adult patient with relapse refractory AML, MDS, or MPD, available haploidentical related donor, and adequate organ functions to undergo reduced intensity allogenic stem cell transplant. The clinical trial will enroll 12-18 subjects in a 3+3 phase I dose escalation fashion over 24 months. Subjects will be followed for 6 months and 1 year following Haplo-Tx.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Biological: Donor Enriched Activated Natural Killer Cell Infusion||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Donor Enriched Activated NK (DEA-NK) Cell Infusion Post Haploidentical Stem Cell Transplant for Refractory Myeloid Malignancies|
|Estimated Study Start Date :||November 1, 2022|
|Estimated Primary Completion Date :||February 1, 2025|
|Estimated Study Completion Date :||February 1, 2025|
Experimental: Donor Enriched Activated NK Infusion (DEA-NK)
Infusion of DEA-NK on day +7 post-transplant
Biological: Donor Enriched Activated Natural Killer Cell Infusion
αβ TCR/CD19 depleted (DEA-NK) cells on day +7 post T-cell replete Haplo-Tx with PTCY
- Feasibility of DEA-NK cell infusions [ Time Frame: 100 Days ]Assess the feasibility of infusing activated enriched donor natural killer cell infusion (DEA-NK) at day +7 post-transplant by the ability to manufacture and administer the DEA-NK cells at study dose levels.
- Safety of DEA-NK cell infusions [ Time Frame: 100 Days ]Assess safety of the DEA-NK cell infusions by recording adverse events experienced by subjects at each dose level.
- Maximum tolerated dose of DEA-NK cell infusions [ Time Frame: 100 Days ]To determine the maximum tolerated dose (MTD) of DEA-NK cell infusion as determined by dose limiting toxicities (DLT) observed.
- Non-Relapse Mortality Rate [ Time Frame: 1 year ]Non-Relapse Mortality (NRM) at 100 days, 180 days and 1 year
- Time to neutrophil recovery [ Time Frame: 21 Days ]Time to neutrophil recovery defined as the first of 3 consecutive days following the nadir that the absolute neutrophil count is at least 500/µl
- Time to platelet recovery [ Time Frame: 21 Days ]Time to platelet recovery defined as the first day that the platelet count is at least 20,000/µl without a transfusion in the preceding 7 days
- Incidence of graft failure [ Time Frame: 35 Days ]Incidence of graft failure as defined by ANC < 500/µl by Day +35 in the absence of disease recurrence
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05375253
|Contact: Marnee Strege, BSNemail@example.com|