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

NCT00089453 | Completed Phase 1

• 1 other identifier: UARK 2003-18
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Myeloma; Transplant; Relapsed; Donor; Stem Cell; Thalidomide; Dexamethasone; Cisplatin; Adriamycin; Cyclophosphamide; Etoposide; Melphalan

Outcome Measures

Primary Outcomes (1)

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

  annually

Secondary Outcomes (1)

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

  annually

Interventions

Dexamethasone DRUG

Dexamthasone 40mg every day, days -5 to -1 only will be given.

Cyclophosphamide DRUG

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.

Melphalan DRUG

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.

Fludarabine DRUG

dose of 1.0mg/m2 on days -8,-5,-2.

Bortezomide DRUG

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

Leukapheresis PROCEDURE

On day 0 to collect donor cells for NK cell isolation

Interleukin DRUG

2 at 3x10x6 IU on days +1 to 13.

Infusion #1 PROCEDURE

Infusion of donor NK Cells #1 on day 0

Leukapheresis #2 PROCEDURE

on day +2

Infusion #2 PROCEDURE

on day +2

Auto Graft PROCEDURE

on day +14

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences/MIRT

Little Rock, Arkansas, 72205, United States

Location

Related Links

• Myeloma Institute for Research \& Therapy website

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

Dexamethasone; Cyclophosphamide; Melphalan; fludarabine; Leukapheresis; Interleukins

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors

Study Officials

• Frits Van Rhee, M.D., Ph.D.

  University of Arkansas for Medical Sciences/MIRT

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2004
• First Posted: August 6, 2004
• Study Start: September 1, 2003
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: April 19, 2012

Record last verified: 2012-04

Locations

US (1)