Multiple MyelomaPhase 1NCT00089453
Study of KIR-Ligand Mismatched Haplo-Identical Natural Killer Cells Transfused Before Autologous Stem Cell Transplant
A Phase 1 study testing Dexamethasone, Cyclophosphamide and Melphalan in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Dexamethasone, Cyclophosphamide and Melphalan
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2003to May 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, 72205
About this study
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
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Dexamethasone, Cyclophosphamide, Melphalan, Fludarabine, Bortezomide
- Keywords
- Myeloma, Transplant, Relapsed, Donor, Stem Cell, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide, Melphalan
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Dexamthasone 40mg every day, days -5 to -1 only will be given.
CyclophosphamideDrug
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.
MelphalanDrug
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.
FludarabineDrug
dose of 1.0mg/m2 on days -8,-5,-2.
BortezomideDrug
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
LeukapheresisProcedure or surgery
On day 0 to collect donor cells for NK cell isolation
InterleukinDrug
2 at 3x10x6 IU on days +1 to 13.
Infusion #1Procedure or surgery
Infusion of donor NK Cells #1 on day 0
Leukapheresis #2Procedure or surgery
on day +2
Infusion #2Procedure or surgery
on day +2
Auto GraftProcedure or surgery
on day +14
What is being measured
The primary outcome is the main question the study is designed to answer.
To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially.
Measured: annually
Secondary outcomes (1)
To establish the response rate, disease free survival , overall survival , and toxicity of regimen.
Measured: annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2004 (estimated)
- Study startSep 2003
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frits Van Rhee, M.D., Ph.D., Principal investigator, University of Arkansas for Medical Sciences/MIRT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00089453
- Sponsor's protocol ID
- UARK 2003-18
- Status last verified
- Apr 2012
- First submitted
- 5 Aug 2004
- Last updated
- 19 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00089453
- Acronym / sponsor ID
- UARK 2003-18
- Conditions
- Multiple Myeloma
- Keywords
- Myeloma, Transplant, Relapsed, Donor, Stem Cell, Thalidomide, Dexamethasone, Cisplatin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- Sep 2003
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 6 Aug 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneDexamthasone 40mg every day, days -5 to -1 only will be given. | Drug | – |
| CyclophosphamideA 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 | – |
| MelphalanMelphalan 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 | – |
| Fludarabinedose of 1.0mg/m2 on days -8,-5,-2. | Drug | – |
| BortezomideA dose of 1.0mg/m2 will be given as a bolus dose on day-8, day-5 and day-2 as per standard practice | Drug | – |
| LeukapheresisOn day 0 to collect donor cells for NK cell isolation | Procedure or surgery | – |
| Interleukin2 at 3x10x6 IU on days +1 to 13. | Drug | – |
| Infusion #1Infusion of donor NK Cells #1 on day 0 | Procedure or surgery | – |
| Leukapheresis #2on day +2 | Procedure or surgery | – |
| Infusion #2on day +2 | Procedure or surgery | – |
| Auto Grafton day +14 | Procedure or surgery | – |
Primary outcome
To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially.
Time frame: annually
1 secondary outcome
To establish the response rate, disease free survival , overall survival , and toxicity of regimen.
Time frame: annually
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2012.
- Myeloma Institute for Research \& Therapy websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frits Van Rhee, M.D., Ph.D. principal investigator
University of Arkansas for Medical Sciences/MIRT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexamethasone, Cyclophosphamide and Melphalan in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To induce anti-myeloma responses in patients with high risk or relapsed myeloma using combination chemo- and immunotherapy comprising sequentially. (time frame: annually). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2012.