Stem Cell Transplantation for Patients With Multiple Myeloma

This study is currently recruiting participants.
Verified March 2014 by University of Chicago
Sponsor:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT01526096
First received: August 10, 2011
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study T Cell Depletion in the Setting of Autologous Stem Cell Transplantation for Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Purity of ex vivo depleted regulatory T cells prior to autologous stem cell transplant (arm 3 only) [ Time Frame: 1-3 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 30
Study Start Date: July 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Alkeran
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 Name: Alkeran
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 Name: Simulect
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 Name: Alkeran
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.

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01526096

Contacts
Contact: Justin Kline, MD 773-702-5550 jkline@medicine.bsd.uchicago.edu

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Justin Kline, MD University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01526096     History of Changes
Other Study ID Numbers: 10-551-B
Study First Received: August 10, 2011
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Basiliximab
JM 3100
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on April 17, 2014