Stem Cell Transplantation for Patients With Multiple Myeloma
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Standard ASCT (Grp 1) Standard autologous stem cell transplantation (ASCT) |
Drug: G-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
Drug: Plerixafor
Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.
Procedure: Apheresis
Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.
Drug: Melphalan
Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.
Other Names:
Procedure: Stem cell re-infusion
Stem cells are thawed and reinfused back into the body via a catheter in the vein.
|
| Experimental: Depletion of T-cells after ASCT (Grp 2) Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood |
Drug: G-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
Drug: Plerixafor
Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.
Procedure: Apheresis
Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.
Drug: Melphalan
Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.
Other Names:
Procedure: Stem cell re-infusion
Stem cells are thawed and reinfused back into the body via a catheter in the vein.
Drug: Basiliximab
Basiliximab (20mg) given by IV infusion (through the vein) 20-30 minutes the day after ASCT.
Other Names:
|
| Experimental: Depletion of T-cells before ASCT(Grp 3) Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant. |
Drug: G-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
Drug: Plerixafor
Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.
Procedure: Apheresis
Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.
Drug: Melphalan
Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.
Other Names:
Procedure: Stem cell re-infusion
Stem cells are thawed and reinfused back into the body via a catheter in the vein.
Device: CliniMACS 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Symptomatic multiple myeloma of any subtype in any disease stage, providing that patient does not have smoldering myeloma.
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Patient must otherwise be a candidate for ASCT as determined by treating physician.
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No current CNS Myeloma at time of enrollment.
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Life expectancy greater than 12 weeks.
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Age greater than or equal to 21 and less than or equal to 70 years old.
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EGOG performance status less than or equal to 2.
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No cardiac, pulmonary, hepatic, or renal contraindications for high dose chemotherapy.
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HIV Negative.
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No active Hepatitis B or C.
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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.
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Use of systemic immunosuppressive medications, including corticosteroids, tacrolimus, mycophenolate mofetil, sirolimus or cyclosporine A.
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Psychiatric illness which may make compliance to the clinical protocol unmanageable or which may compromise the ability of the patient to give informed consent.
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Active autoimmune disease including but not limited to: rheumatoid arthritis inflammatory bowel disease, celiac disease, systemic lupus erythematosis, scleroderma or multiple sclerosis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Chicago | Chicago | Illinois | United States | 60637 |
Sponsors and Collaborators
- University of Chicago
Investigators
- Principal Investigator: Michael Bishop, MD, University of Chicago
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 10-551-B