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Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL

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: NCT00490529
Recruitment Status : Completed
First Posted : June 22, 2007
Last Update Posted : September 19, 2019
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Ronald Levy, Stanford University

Brief Summary:
Mantle Cell Lymphoma is a sub-type of Non-Hodgkin's Lymphoma which is generally considered incurable with current therapy. Participants will receive an autologous vaccine against their individual lymphoma after undergoing stem cell transplantation. This vaccination may prolong the time which patients will stay in remission from their disease.

Condition or disease Intervention/treatment Phase
Lymphoma, Mantle-Cell Biological: CpG-MCL vaccine Procedure: Vaccine-primed T-cells Drug: PF-3512676 Procedure: Autologous peripheral blood stem cell (PBSC) transplant Drug: Rituximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1-2 Study of a CpG-Activated Whole Cell Vaccine Followed by Autologous "Immunotransplant" for Mantle Cell Lymphoma
Study Start Date : August 2009
Actual Primary Completion Date : December 14, 2017
Actual Study Completion Date : December 14, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: CpG-MCL vaccine
Participants will initially receive three "priming" CpG-MCL vaccinations in 21 days at 4 to 7 day intervals, followed by collection of "primed" T-Cells. Subsequently, within 72 hours of autologous peripheral blood stem cell (PBSC) transplant (a standard of care procedure), each participant will receive his/her CpG-MCL vaccine and re-infusion of vaccine-primed T-cells ("immuno-transplant"). At ≥ 3 months after AHCT, when medically feasible, the patient will receive the final CpG-MCL vaccine. Regular follow-up research analysis of molecular residual disease will continue for 3 years or until disease progression.
Biological: CpG-MCL vaccine

The CpG-MCL vaccine is a suspension of the participant's mantle cell lymphoma (MCL), that have been cultured for 72 hours with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. Aliquots are frozen prior to use.

At each of 3 vaccination time points, 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection in the patient's lateral thigh.

Other Names:
  • CpG-activated, autologous tumor vaccine
  • Cytosine-Guanosine repeats (CpG)-mantle cell lymphoma (CpG-MCL vaccine)

Procedure: Vaccine-primed T-cells
Vaccine primed T-cells are a leukapheresis harvest of peripheral blood mononuclear cells (PMPC). Each collection will be approximately 1 x 10e10 CD3+ T-cells.

Drug: PF-3512676

PF-03512676 is an immunostimulatory single-stranded oligodeoxynucleotide containing unmethylated cytosine and guanine (CpG) motifs and synthesized with a nuclease-resistant phosphorothioate backbone

With each CpG-MCL vaccination, participants will receive a concurrent subcutaneous injection of PF-3512676 as an adjuvant.

Other Name: CPG-7909

Procedure: Autologous peripheral blood stem cell (PBSC) transplant
Regular medical care procedure
Other Name: Hematopoietic stem cell transplantn (HSCT)

Drug: Rituximab
375 mg/m² by intravenous (IV) infusion
Other Names:
  • Rituxan
  • MabThera




Primary Outcome Measures :
  1. Freedom from Molecular residual disease (MRD) Post-autologous Stem Cell Transplant (ASCT) [ Time Frame: 12 months ]
    Molecular residual disease (MRD) is defined as detection in blood samples by the ClonoSEQ test of the (11;14) (q13;q32) gene translocation. It is considered positive if a tumor-specific VDJ sequence is detected in the peripheral blood cells by Ig-HTS at a frequency of greater or equal to 1 molecule per 10,000 input leukocyte equivalents of DNA within 1 year post-autologous stem cell transplant (ASCT). The outcome will be reported as number and percent of participants that maintain MRD-negative status (ie, 1-year freedom from MRD). This outcome is reported as a number without dispersion.


Secondary Outcome Measures :
  1. Time to Progression (TTP) [ Time Frame: 5 years ]

    Time to progression (TTP) is measured from the time of autologous stem cell transplantation (ASCT) until the cancer progresses or relapses. Progression is assessed based on CT imaging per the Cheson Criteria (2008). Progression per the Cheson Criteria is defined as having occurred when the sum of tumor lesion dimensions is ≥ 150% of the baseline value. The outcome is reported the median and full range only for those patients that experienced progression or relapse.

    15 subject Those patients that did not experience progression or relapse are not included.

    Data unclear, need to talk with Ami.


  2. Overall survival (OS) rate [ Time Frame: After 1, 2, 3, 4, and 5 years ]
    Overall survival (OS) rate is defined as percentage of participants alive after the date of transplant. The outcome will be reported as number and percentage of participants remaining alive each year, through 5 years (reported as a number without dispersion).

  3. Detection of Tumor-specific CD8 memory T-cells before and after vaccination [ Time Frame: 5 years ]

    Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells.

    The outcome is reported as the number of participants for whom tumor-specific memory CD8 cells were detected at baseline and after transplant (numbers without dispersion) 31/14 of 35


  4. Detection of Tumor-specific CD4 T-cells before and after vaccination [ Time Frame: 5 years ]

    Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells.

    The outcome is reported as the number of participants for whom tumor-specific memory CD4 cells were detected at baseline and after transplant (numbers without dispersion) 20/14 of 35




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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  • Newly-diagnosed with mantle cell lymphoma (MCL) with accessible disease site for excisional biopsy, OR have sufficient peripheral blood tumor to leukapherese ≥ 1.5 x 10e9 lymphoma cells in a single session
  • Medically appropriate by standard clinical criteria to receive rituximab and standard induction chemotherapy and high-dose chemotherapy with autologous hematopoietic cell transplant (AHCT)
  • HIV-negative
  • Eastern Cooperative Oncology Group (ECOG) Performance Status, OR Karnofsky performance scale 50 to 100%
  • Capable of providing informed consent

EXCLUSION CRITERIA

  • Currently receiving immunosuppressive medications
  • Severe psychological or medical illness
  • Pregnant or lactating
  • Unable to safely complete the study, at the discretion of the principal investigator

Information from the National Library of Medicine

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): NCT00490529


Locations
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United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Ronald Levy
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Ronald Levy, MD Stanford University

Publications:
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Responsible Party: Ronald Levy, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT00490529     History of Changes
Other Study ID Numbers: IRB-05089
LYMNHL0040-BMT212 ( Other Identifier: OnCore )
96940 ( Other Identifier: Stanford University Alternate IRB Approval Number )
IRB-5089 ( Other Identifier: Stanford IRB )
NCI-2011-00136 ( Other Identifier: NCI Trial ID )
First Posted: June 22, 2007    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antirheumatic Agents