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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dexamethasone
Cyclophosphamide
Melphalan
Fludarabine
Bortezomide
Leukapheresis
Interleukin
Infusion #1
Leukapheresis #2
Infusion #2
Auto Graft
Sponsored by
University of Arkansas
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Myeloma, Transplant, Relapsed, Donor, Stem Cell, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide, Melphalan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Arkansas for Medical Sciences/MIRT

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 5, 2004
Last Updated
April 17, 2012
Sponsor
University of Arkansas
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1. Study Identification

Unique Protocol Identification Number
NCT00089453
Brief Title
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

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
September 2003 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Myeloma, Transplant, Relapsed, Donor, Stem Cell, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide, Melphalan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamthasone 40mg every day, days -5 to -1 only will be given.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
dose of 1.0mg/m2 on days -8,-5,-2.
Intervention Type
Drug
Intervention Name(s)
Bortezomide
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Leukapheresis
Intervention Description
On day 0 to collect donor cells for NK cell isolation
Intervention Type
Drug
Intervention Name(s)
Interleukin
Intervention Description
2 at 3x10x6 IU on days +1 to 13.
Intervention Type
Procedure
Intervention Name(s)
Infusion #1
Intervention Description
Infusion of donor NK Cells #1 on day 0
Intervention Type
Procedure
Intervention Name(s)
Leukapheresis #2
Intervention Description
on day +2
Intervention Type
Procedure
Intervention Name(s)
Infusion #2
Intervention Description
on day +2
Intervention Type
Procedure
Intervention Name(s)
Auto Graft
Intervention Description
on day +14
Primary Outcome Measure Information:
Title
To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially.
Time Frame
annually
Secondary Outcome Measure Information:
Title
To establish the response rate, disease free survival , overall survival , and toxicity of regimen.
Time Frame
annually

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frits Van Rhee, M.D., Ph.D.
Organizational Affiliation
University of Arkansas for Medical Sciences/MIRT
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences/MIRT
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States

12. IPD Sharing Statement

Links:
URL
http://myeloma.uams.edu/
Description
Myeloma Institute for Research & Therapy website

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

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