Myeloma
Conditions
Brief summary
The purpose of this study is to test whether regulatory T-cell reduction is possible and safe in myeloma subjects undergoing autologous stem cell transplantation (ASCT).
Interventions
DRUGG-CSF
G-CSF will be self-administered shot daily for 4 days pre-transplant. Up to 8 doses of G-CSF may be given. G-CSF will also be administered once daily under the skin beginning 5 days after your stem cell infusion until your white blood cell count is high enough
DRUGPlerixafor
Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.
PROCEDUREApheresis
Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.
DRUGMelphalan
Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.
PROCEDUREStem cell re-infusion
Stem cells are thawed and reinfused back into the body via a catheter in the vein.
DRUGBasiliximab
Basiliximab (20mg) given by IV infusion (through the vein) 20-30 minutes the day after ASCT.
DEVICECliniMACS CD25 microbeads and cell sorter
The stem cells collected during apheresis will be counted and treated with CD25 microbeads and processed by a special device called a CliniMACs machine which removes the regulatory T cells from you stem cell product.
Sponsors
University of Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Symptomatic multiple myeloma of any subtype in any disease stage, providing that patient does not have smoldering myeloma. * Patient must otherwise be a candidate for ASCT as determined by treating physician. * No current CNS Myeloma at time of enrollment. * Life expectancy greater than 12 weeks. * Age greater than or equal to 21 and less than or equal to 70 years old. * EGOG performance status less than or equal to 2. * No cardiac, pulmonary, hepatic, or renal contraindications for high dose chemotherapy. * HIV Negative. * No active Hepatitis B or C. * Patients must be able to provide written informed, consent.
Exclusion criteria
* Pregnant or nursing women. Women of child-bearing age must be tested for pregnancy. * Use of systemic immunosuppressive medications, including corticosteroids, tacrolimus, mycophenolate mofetil, sirolimus or cyclosporine A. * Psychiatric illness which may make compliance to the clinical protocol unmanageable or which may compromise the ability of the patient to give informed consent. * Active autoimmune disease including but not limited to: rheumatoid arthritis inflammatory bowel disease, celiac disease, systemic lupus erythematosis, scleroderma or multiple sclerosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Purity of ex vivo depleted regulatory T cells prior to autologous stem cell transplant (arm 3 only) | 1-3 days | Percentage of CD4+CD25+ regulatory T cells following ex vivo depletion in arm 3 will be analyzed by flow cytometry and compared to a pre-CD25-depletion sample. The depletion of CD25+ cells among the entire CD4+ population is expected to reach 80% efficiency. |
| Timing and duration of regulatory T cell depletion and recovery following autologous stem cell transplant | 180 days | Timing and duration of regulatory T cell depletion and recovery following in vivo or ex vivo (arms 2 and 3) CD25+ T cell depletion will be performed at pre-defined timepoints prior to and following autologous stem cell transplant by flow cytometry on peripheral blood samples and directly compared to the percentages of regulatory T cells (CD4+CD25+FoxP3+ or CD4+CD25+CD127-) present at the same timepoints in patients enrolled onto arm 1 in which no regulatory T cell depletion is performed. |
| Incidence of autologous graft-versus-host disease following in vivo or ex vivo regulatory T cell depletion | 180 days | The indicence of autologous graft-versus-host disease, as assessed by the development of skin rash, diarrhea and/or liver function test abnormalities consistent with autologous graft-versus-host disease following CD25+ T cell depletion and autologous stem cell transplant compared with the incidence of autologous graft-versus-host disease in patients enrolled onto arm 1 in which no regulatory T cell depletion is performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kinetics of recovery of peripheral blood cellular elements | 180 days | Time to recovery of neutrophils and platelets will be analyzed by daily complete blood counts following autologous stem cell transplant. Patients enrolled onto arms 2 and 3 (in vivo and ex vivo regulatory T cell depletion, respectively) will be directly compared to patients enrolled onto arm 1 in which no regulatory T cell depletion is performed. |
| Number of patients that experience a complete response following autologous stem cell transplant based upon the assigned study arm using International Myeloma Working Group definitions | 100 days | The complete response rate following autologous stem cell transplant with or without regulatory T cell depletion will be analyzed and compared directly between study arms. |
Countries
United States
Outcome results
None listed