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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard ASCT (Grp 1) | Active Comparator | Standard autologous stem cell transplantation (ASCT) |
|
| Depletion of T-cells after ASCT (Grp 2) | Experimental | Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood |
|
| Depletion of T-cells before ASCT(Grp 3) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| G-CSF | Drug | 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 |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Bishop, MD | University of Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago | Chicago | Illinois | 60637 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31940591 | Derived | Derman BA, Zha Y, Zimmerman TM, Malloy R, Jakubowiak A, Bishop MR, Kline J. Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study. J Immunother Cancer. 2020 Jan;8(1):e000286. doi: 10.1136/jitc-2019-000286. |
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| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| C088327 | plerixafor |
| D001781 | Blood Component Removal |
| D008558 | Melphalan |
| D000077552 | Basiliximab |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
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| Plerixafor | Drug | Plerixafor (self-administered shot)prior to the beginning of the stem cell collection. Up to 4 doses of plerixafor may be given. |
|
| Apheresis | Procedure | Stem cell collection begins on day 5 and can last up to 3 days depending on the number collected. |
|
| Melphalan | Drug | Melphalan chemotherapy 100mg/m2 for 2 days after your admission into the hospital for your ASCT procedure. |
|
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| Stem cell re-infusion | Procedure | Stem cells are thawed and reinfused back into the body via a catheter in the vein. |
|
| Basiliximab | Drug | Basiliximab (20mg) given by IV infusion (through the vein) 20-30 minutes the day after ASCT. |
|
|
| CliniMACS CD25 microbeads and cell sorter | Device | 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. |
|
| 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 |
| D016298 |
| Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D013812 | Therapeutics |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |