Stem Cell Transplantation for Patients With Multiple Myeloma

Study Overview
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Brief Summary
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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).

Official Title
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Pilot Study T Cell Depletion in the Setting of Autologous Stem Cell Transplantation for Patients With Multiple Myeloma

Conditions
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Myeloma

Intervention / Treatment
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* Drug: G-CSF
* Drug: Plerixafor
* Procedure: Apheresis
* Drug: Melphalan
* Procedure: Stem cell re-infusion
* Drug: Basiliximab
* Device: CliniMACS CD25 microbeads and cell sorter


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard ASCT (Grp 1)<br>Standard autologous stem cell transplantation (ASCT) | Drug: G-CSF<br>* 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<br>Drug: Plerixafor<br>* Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.<br>Procedure: Apheresis<br>* Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.<br>Drug: Melphalan<br>* Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.<br>* Other names: Alkeran;Procedure: Stem cell re-infusion<br>* Stem cells are thawed and reinfused back into the body via a catheter in the vein.<br>|
| Experimental: Depletion of T-cells after ASCT (Grp 2)<br>Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood | Drug: G-CSF<br>* 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<br>Drug: Plerixafor<br>* Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.<br>Procedure: Apheresis<br>* Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.<br>Drug: Melphalan<br>* Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.<br>* Other names: Alkeran;Procedure: Stem cell re-infusion<br>* Stem cells are thawed and reinfused back into the body via a catheter in the vein.<br>Drug: Basiliximab<br>* Basiliximab (20mg) given by IV infusion (through the vein) 20-30 minutes the day after ASCT.<br>* Other names: Simulect;|
| Experimental: Depletion of T-cells before ASCT(Grp 3)<br>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<br>* 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<br>Drug: Plerixafor<br>* Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given.<br>Procedure: Apheresis<br>* Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected.<br>Drug: Melphalan<br>* Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure.<br>* Other names: Alkeran;Procedure: Stem cell re-infusion<br>* Stem cells are thawed and reinfused back into the body via a catheter in the vein.<br>Device: CliniMACS CD25 microbeads and cell sorter<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Purity of ex vivo depleted regulatory T cells prior to autologous stem cell transplant (arm 3 only) | 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. | 1-3 days | 
| Timing and duration of regulatory T cell depletion and recovery following autologous stem cell transplant | 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. | 180 days | 
| Incidence of autologous graft-versus-host disease following in vivo or ex vivo regulatory T cell depletion | 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. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics of recovery of peripheral blood cellular elements | 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. | 180 days | 
| 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 | 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. | 100 days |