Clinical trial NCT00089453: Study of KIR-Ligand Mismatched Haplo-Identical Natural Killer Cells Transfused Before Autologous Stem Cell Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Myeloma
Transplant
Relapsed
Donor
Stem Cell
Thalidomide
Dexamethasone
Cisplatin
Adriamycin
Cyclophosphamide
Etoposide
Melphalan
Lead sponsor: University of Arkansas
Sponsor class: OTHER
First posted: 2004-08-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially.
timeFrame: annually
Secondary outcomes:
measure: To establish the response rate, disease free survival , overall survival , and toxicity of regimen.
timeFrame: annually
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences/MIRT
state: Arkansas
Study officials:
affiliation: University of Arkansas for Medical Sciences/MIRT
name: Frits Van Rhee, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: