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

Sponsor

University of Arkansas (Other)

Overall Status

Completed

CT.gov ID

NCT00089453

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Dexamethasone Drug: Cyclophosphamide Drug: Melphalan Drug: Fludarabine Drug: Bortezomide Procedure: Leukapheresis Drug: Interleukin Procedure: Infusion #1 Procedure: Leukapheresis #2 Procedure: Infusion #2 Procedure: Auto Graft	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2003

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

May 1, 2010

Outcome Measures

Primary Outcome Measures

To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially. [annually]

Secondary Outcome Measures

To establish the response rate, disease free survival , overall survival , and toxicity of regimen. [annually]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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