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

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.

Conditions

• Multiple Myeloma

Interventions

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

Sponsors & Collaborators

• University of Arkansas

  lead OTHER

Principal Investigators

• Frits Van Rhee, M.D., Ph.D. · University of Arkansas for Medical Sciences/MIRT

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2003-09-30

Primary Completion

2010-05-31

Completion

2010-05-31

Countries

• United States

Study Locations