Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00566098|
Recruitment Status : Completed
First Posted : December 3, 2007
Results First Posted : December 19, 2018
Last Update Posted : December 19, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma and Plasma Cell Neoplasm||Biological: MILs Drug: Melphalan Biological: PCV13||Phase 1 Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma|
|Actual Study Start Date :||November 2007|
|Actual Primary Completion Date :||June 2014|
|Actual Study Completion Date :||October 2018|
Autologous stem cell transplant with a conditioning regimen of melphalan 100 mg/m^2 on each of Days -2 and -1. Infusion of activated marrow infiltrating lymphocytes (MILs) on Day 3. PCV13 vaccine will be given before and/or after Day 0 depending on when participants are enrolled.
Other Name: Alkeran
Other Name: Prevnar
- Hematopoietic Engraftment [ Time Frame: Up to 1 year ]Days to absolute neutrophil count > 500 cells per microliter.
- Disease Response [ Time Frame: Up to 2 years ]Percentage of participants with partial or complete response by Bladé criteria. Partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
- Feasibility of MILs Generation as Assessed by Percentage of Participants With Successful MIL Generation [ Time Frame: Up to 1 year ]Success rate of expanding MILs in vitro and obtaining a protocol-specified product.
- T-cell Reconstitution as Determined by Absolute Lymphocyte Count (ALC) [ Time Frame: Days 14, 28, 60, 180, and 360 ]ALC counts trending over time.
- Survival [ Time Frame: Up to 129 months ]Survival in months for participants who are alive (Overall Survival) and alive without disease progression (Progression-free survival). Disease progression is defined as a change from negative to positive on immunofixation or electrophoresis for participants previously in complete remission or a 25% increase in serum electrophoresis for participants not previously in complete remission. Partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
- Pneumococcal-specific Vaccine Responses [ Time Frame: At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant ]CRM-197 Prevnar-specific vaccine responses that measure the T-cell response of the vaccine quantified as %CD3+/CFSE-low/IFN-gamma+.
- Anti-tumor Immune Responses [ Time Frame: At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant ]Myeloma lysate response that measures the T-cell response quantified as %CD3+/CFSE-low/IFN-gamma+.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 at Johns Hopkins|