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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00089453
First received: August 5, 2004
Last updated: April 17, 2012
Last verified: April 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially. [ Time Frame: annually ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To establish the response rate, disease free survival , overall survival , and toxicity of regimen. [ Time Frame: annually ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: September 2003
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089453

Locations
United States, Arkansas
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Frits Van Rhee, M.D., Ph.D. University of Arkansas for Medical Sciences/MIRT
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00089453     History of Changes
Other Study ID Numbers: UARK 2003-18
Study First Received: August 5, 2004
Last Updated: April 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
Myeloma
Transplant
Relapsed
Donor
Stem Cell
Thalidomide
Dexamethasone
Cisplatin
Adriamycin
Cyclophosphamide
Etoposide
Melphalan

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Melphalan
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014