Activated White Blood Cells in Treating Patients Undergoing an Autologous Stem Cell Transplant for Newly Diagnosed Stage II or Stage III Multiple Myeloma
RATIONALE: Activating white blood cells in the laboratory may help them kill more cancer cells when they are put back in the body. This may be an effective treatment for patients undergoing a stem cell transplant for multiple myeloma.
PURPOSE: This phase I/II trial is studying the side effects of activated white blood cells and to see how well they work in treating patients who are undergoing a stem cell transplant for newly diagnosed stage II or stage III multiple myeloma.
Multiple Myeloma and Plasma Cell Neoplasm
Biological: therapeutic autologous lymphocytes
Biological: therapeutic tumor infiltrating lymphocytes
Procedure: autologous hematopoietic stem cell transplantation
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma|
- Toxicity [ Designated as safety issue: Yes ]
- Hematopoietic engraftment [ Designated as safety issue: No ]
- Response rates utilizing the Blade criteria, including complete response (CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate, partial response (PR) rate, minimal response (MR) rate, overall response rate (CR, VGPR, ... [ Designated as safety issue: No ]
- Generation of activated marrow infiltrating lymphocytes (aMILs) [ Designated as safety issue: No ]
- T-cell reconstitution, including absolute lymphocyte counts, CD3+/ CD4+/ CD8+ T-cell counts [ Designated as safety issue: No ]
- Progression-free survival and overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Pneumococcal-specific vaccine responses [ Designated as safety issue: No ]
- Anti-tumor immune responses [ Designated as safety issue: No ]
- Delayed-type hypersensitivity (DTH) responses [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
- Evaluate the safety and response rate of activated marrow infiltrating lymphocytes (aMILs) in patients undergoing autologous peripheral blood stem cell transplantation for newly diagnosed, stage II-III multiple myeloma.
- Determine the overall in vitro fold-expansion and assess pre- and post-expansion for myeloma T-cell specificity in assessing the feasibility of generating aMILs from myeloma patients.
- Assess the toxicity of aMILs.
- Evaluate the effect of aMILs on hematopoietic engraftment, including neutrophil engraftment, platelet engraftment, and primary graft failure (if failure occurs).
- Evaluate response rates utilizing the Blade criteria, including the complete response (CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate, partial response (PR) rate, minimal response (MR) rate, and overall response rate (CR, VGPR, PR, MR).
- Evaluate T-cell reconstitution, including absolute lymphocyte counts, CD3+, CD4+, and CD8+ T-cell counts.
- Evaluate progression-free survival and overall survival.
- Evaluate anti-tumor immune response.
- Determine pneumococcal-specific vaccine responses.
- Determine delayed-type hypersensitivity (DTH) responses.
OUTLINE: Patients undergo collection of marrow infiltrating lymphocytes (MILs)* either at diagnosis prior to the initiation of induction therapy or upon completion of induction therapy. The MILs bone marrow product undergo ex vivo activation and expansion of T cells for 7-8 days to produce activated marrow infiltrating lymphocytes (aMILs). Patients then undergo stem cell mobilization and leukapheresis to collect the peripheral blood stem cells 12 days after mobilization. Patients receive melphalan IV over 20-30 minutes on days -2 and -1 and undergo a peripheral blood stem cell transplantation on day 0 as planned. Patients receive aMILs infusion on day 3. Patients receive pneumococcal polyvalent vaccine on day 21.
NOTE: *Patients who have completed induction therapy receive pneumococcal polyvalent vaccine approximately 2 weeks prior to MILs collection; patients undergoing MILs collection prior to starting induction therapy do not receive a pre-transplantation vaccine.
Blood and bone marrow samples are collected periodically for laboratory correlative studies.
After completion of study treatment, patients are followed periodically for up to 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00566098
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Study Chair:||Ivan Borrello, MD||Sidney Kimmel Comprehensive Cancer Center|