Study of KIR-Ligand Mismatched Haplo-Identical Natural Killer Cells Transfused Before Autologous Stem Cell Transplant
This study has been completed.
Sponsor:
University of Arkansas
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
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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:
MedlinePlus related topics:
Multiple Myeloma
Drug Information available for:
Dexamethasone
Cyclophosphamide
Melphalan
Dexamethasone acetate
Dexamethasone sodium phosphate
Melphalan hydrochloride
Fludarabine
Fludarabine phosphate
U.S. FDA Resources
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:
Detailed Description:
-
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
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
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 Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Cyclophosphamide |
Melphalan Fludarabine monophosphate Fludarabine Dexamethasone Dexamethasone acetate Dexamethasone 21-phosphate BB 1101 Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents |
ClinicalTrials.gov processed this record on May 16, 2013