NCT00089453

Study of KIR-Ligand Mismatched Haplo-Identical Natural Killer Cells Transfused Before Autologous Stem Cell Transplant

UARK 2003-18, A Phase II Study of KIR-Ligand Mismatched Haplo-Identical Natural Killer Cells Transfused Before Autologous Stem Cell Transplant in Relapsed Multiple Myeloma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University of Arkansas · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially: 1) lymphoid and myeloid suppressive conditioning, 2) adoptive transfer of purified KIR-ligand mismatched Natural Killer cells from a haplo-identical donor, and 3) autografting two weeks after infusion of NK cells to ensure autologous reconstitution. Other objectives include establishing the response rate, disease free survival, progression free survival and toxicity of regimen. Secondary objectives are to monitor the persistence of haplo-identical purified KIR-ligand mismatched Natural Killer cells by molecular methods, select haplo-identical purified KIR-ligand mismatched donors and predict prior to therapy which donor will induce a response, monitor Natural Killer cell reconstitution prior to and after autografting, and establish Natural Killer cell clones after autografting and determine origin and specificity.

Detailed description

This study will induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially: 1) lymphoid suppressive conditioning to avoid rejection of the donor NK cells, 2) adoptive transfer of purified KIR-ligand mismatched Natural Killer cells from a haplo-identical donor, and 3) autografting two weeks after infusion of NK cells to ensure autologous reconstitution.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Dexamethasone	Dexamthasone 40mg every day, days -5 to -1 only will be given.
DRUG	Cyclophosphamide	A dose of 60mg/kg (using calculated body weight - see appendix A.) will be infused on day-3, and -2. Cyclophosphamide is administered by intravenous infusion over 2-4 hrs in 250 mLs of Normal Saline (0.9%) or D5W Standard MESNA (60% or 36mg/kg) protection to prevent hemorrhagic cystitis will be given on day -3, -2 and -1.
DRUG	Melphalan	Melphalan will be given as a single dose of 140mg/m2 on day -1. Subject weighing more than 60kg will be dosed according to their calculated body weight.Melphalan will be diluted in normal saline(0.9%NaCl) to a concentration of 1.5mg/ml. A dose of 140mg/m2 will be administered intravenously over a period \<or= 20 minutes on day -1.
DRUG	Fludarabine	dose of 1.0mg/m2 on days -8,-5,-2.
DRUG	Bortezomide	A dose of 1.0mg/m2 will be given as a bolus dose on day-8, day-5 and day-2 as per standard practice
PROCEDURE	Leukapheresis	On day 0 to collect donor cells for NK cell isolation
DRUG	Interleukin	2 at 3x10x6 IU on days +1 to 13.
PROCEDURE	Infusion #1	Infusion of donor NK Cells #1 on day 0
PROCEDURE	Leukapheresis #2	on day +2
PROCEDURE	Infusion #2	on day +2
PROCEDURE	Auto Graft	on day +14

Timeline

• Start date: 2003-09-01
• Primary completion: 2010-05-01
• Completion: 2010-05-01
• First posted: 2004-08-06
• Last updated: 2012-04-19

Locations

1 site across 1 country: United States