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Trial record 3 of 2545 for:    "Plasma Cell Neoplasm"

Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00566098
Recruitment Status : Completed
First Posted : December 3, 2007
Results First Posted : December 19, 2018
Last Update Posted : December 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE November 30, 2007
First Posted Date  ICMJE December 3, 2007
Results First Submitted Date  ICMJE September 14, 2018
Results First Posted Date  ICMJE December 19, 2018
Last Update Posted Date December 19, 2018
Actual Study Start Date  ICMJE November 2007
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 30, 2007)
  • Toxicity
  • Hematopoietic Engraftment
  • 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 ..
  • Generation of activated marrow infiltrating lymphocytes (aMILs)
Change History Complete list of historical versions of study NCT00566098 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
  • 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+.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2007)
  • T-cell reconstitution, including absolute lymphocyte counts, CD3+/ CD4+/ CD8+ T-cell counts
  • Progression-free survival and overall survival
  • Pneumococcal-specific Vaccine Responses
  • Anti-tumor Immune Responses
  • Delayed-type hypersensitivity (DTH) responses
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma
Official Title  ICMJE Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma
Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

  • 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).

Secondary

  • 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma and Plasma Cell Neoplasm
Intervention  ICMJE
  • Biological: MILs
    Other Names:
    • Marrow infiltrating lymphocytes
    • Activated marrow infiltrating lymphocytes
    • aMILs
  • Drug: Melphalan
    Other Name: Alkeran
  • Biological: PCV13
    Other Name: Prevnar
Study Arms  ICMJE Experimental: ASCT+MILs
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.
Interventions:
  • Biological: MILs
  • Drug: Melphalan
  • Biological: PCV13
Publications * Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, Ferguson A, Emerling A, Luznik L, Matsui W, Powell J, Fuchs E, Rosner GL, Epstein C, Rudraraju L, Ambinder RF, Jones RJ, Pardoll D, Borrello I. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015 May 20;7(288):288ra78. doi: 10.1126/scitranslmed.aaa7014.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 29, 2018)
26
Original Enrollment  ICMJE
 (submitted: November 30, 2007)
15
Actual Study Completion Date  ICMJE October 2018
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Newly diagnosed disease
    • Durie-Salmon stage II or III disease
  • Measurable disease, defined by any of the following:

    • Measurable serum and/or urine M-protein levels documented and available prior to induction therapy
    • Positive serum free light chain assay
  • Must have completed a minimum of 3 courses of myeloma specific therapy
  • Candidate for autologous stem cell transplantation
  • Patients who have achieved a complete remission at the time of bone marrow harvest for marrow infiltrating lymphocytes (MILs) expansion are not eligible
  • No evidence of spinal cord compression
  • Diagnosis of the following cancers are not allowed:

    • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
    • Non-secretory myeloma (no measurable protein on serum free light chain assay)
    • Plasma cell leukemia
  • No amyloidosis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 6 months
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and up to day 180
  • Corrected serum calcium < 11 mg/dL and no evidence of symptomatic hypercalcemia
  • Total bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • ALT ≤ 2.0 times ULN
  • Serum creatinine < 2.0 mg/dL
  • No history of other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer
  • No history of autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus) requiring systemic treatment

    • Hypothyroidism without evidence of Graves' disease or Hashimoto thyroiditis is allowed
  • No infection requiring treatment with antibiotics, antifungal, or antiviral agents within the past 7 days
  • No HIV infection
  • No major organ system dysfunction including, but not limited to, the following:

    • New York Heart Association class III or IV congestive heart failure
    • Pulmonary disease requiring the use of inhaled steroids or bronchodilators
    • Renal, hepatic, gastrointestinal, neurologic, or psychiatric dysfunction that would impair ability to participate in the study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior hematopoietic stem cell transplantation
  • At least 3 weeks since prior corticosteroids (i.e., glucocorticoids)
  • At least 3 weeks since prior myeloma-specific therapy
  • At least 4 weeks since participation in any clinical trial that involved an investigational drug or device
  • No concurrent therapy with any of the following:

    • Corticosteroids (e.g., hydrocortisone, prednisone, prednisolone, dexamethasone [Decadron])

      • Inhaled steroids used for treatment of allergic rhinitis or pulmonary disease allowed
    • Thalidomide
    • Interferon
    • Growth factors, interleukins, or other cytokines (except filgrastim [G-CSF] as outlined in the protocol, or erythropoietin)
    • Cytotoxic chemotherapy agents (except cyclophosphamide for stem cell mobilization and high-dose melphalan)
    • Immunosuppressive drugs
    • Experimental therapies
    • Radiotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00566098
Other Study ID Numbers  ICMJE J0770
P30CA006973 ( U.S. NIH Grant/Contract )
NA_00012038 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Ivan Borrello, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP