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

Inclusion Criteria:

- MM in frank relapse after a single or tandem transplant or high risk Myeloma

- Patients with prior transplant must be more than 4 months after the last transplant

- Karnofsky performance score >or =70, or a performance score of 50-70 exclusively due
to bone pain caused by myeloma

- 18 years of age or older

- An expected survival greater than 3 months

- ANC >1,000/microliters, platelet count > 100,000/microliters

- Donor and patient must have signed an IRB-approved consent and been informed about
the investigational nature of the study

- Donor must have negative serology for HIV

- Available haplo-identical family donor fit to undergo leukapheresis and mismatched
for KIR-ligand(s) with the patient in the graft-versus host direction.

- Stored cells for autografting of at least 30 million CD34+ cells/kg

- Back-up cells of at least 20 million CD34+ cells/kg in case of non-engraftment.

- There must be an unambiguous marker for response to therapy in the first ten
patients. Therefore the patient must have detectable and quantifiable M-protein or
light chain excretion in urine, light chain quantification in serum (FREELITE) or
clear radiological signal lesion(s) in order to be eligible

- After 10 relapsed patients have been treated and toxicity is deemed acceptable,
high-risk myeloma (defined as the presence of abnormal cytogenetics or metaphase
analysis) patients without relapse can be entered

Exclusion Criteria:

- Intravenous chemotherapy or antibody therapy affecting T-lymphocytes and/or natural
killer cells e.g. cyclophosphamide, melphalan, ATG, Campath-1H etc. within the past 2
weeks prior to commencement of conditioning. Last therapy is less than 14 days prior
to starting fludarabine

- Fever or active infection, requiring IV antibiotics

- Liver function: total bilirubin > 2xULN or AST/ALT >3xULN

- Renal function: patients on dialysis