Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL
Condition: Lymphoma, Mantle-Cell
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Mantle cell lymphoma (MCL) is a sub-type of non-Hodgkin's lymphoma (NHL) 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.
    

Detailed description: 
      Study treatment is a complex set of steps of research procedures and regular medical care. By
      using a participant's cancer cells as an immungen, the study hopes to improve freedom from
      molecular residual disease (MRD).

      PRIMARY OBJECTIVE Freedom from molecular residual disease at 1-year post-autologous
      transplant.

      SECONDARY OBJECTIVE Time To Clinical Progression (TTP)

      This study has 2 research agents, PF-03152676 and CpG-MCL Vaccine.

      PF-03152676 is a synthetic DNA molecule, 24 nucleotides in length with a nuclease-resistant
      phosphorothioate backbone. It is an immunostimulatory, single-stranded oligodeoxynucleotide
      (oligo-DNA) containing unmethylated cytosine and guanine (CpG) motifs and synthesized with a
      nuclease-resistant phosphorothioate backbone. PF-03512676 acts as an agonist of human
      Toll-like receptor 9, leading to activation of antigen-presenting cells and a cascade of
      anti-tumor immune reactions.

      CpG-MCL Vaccine is the primary study agent. It is prepared by dissociating a participant's
      harvested tumor cells into a single-cell suspension, and culturing them with PF-03152676 for
      72 hours at 37 degrees C, 5% CO2 to allow for up-regulation of antigen-presenting and
      co-stimulatory molecules, then irradiated to 200 Gy to destroy any remaining cancer
      propagating ability.

      The study procedure is summarized as 12 steps, listed below.

        -  Step 1. Undergo excisional tumor biopsy or apheresis to obtain tumor cells, which will
           be used to generate the CpG-MCL vaccine .

        -  Step 2. Receive standard induction chemotherapy (regular medical care).

        -  Step 3. Once in remission, receive 3 vaccinations of CpG-MCL Vaccine over 3 weeks. With
           each CpG-MCL vaccination, a concurrent subcutaneous injection of PF-3512676 is
           administered as an adjuvant.

        -  Step 4. About 4 weeks later, receive rituximab 375 mg/m² to minimize any residual tumor.

        -  Step 5. Apheresis procedure to harvest the CpG-MCL Vaccine-primed T-cells. Each
           collection is ~1 x 10e10 CD3+ T-cells.

        -  Step 6. High-dose cytoxan and filgrastim to mobilize peripheral blood progenitor cell
           (PBPC).

        -  Step 7. Undergo separate apheresis procedure to harvest PBPC).

        -  Step 8. Receive myeloablative chemotherapy (regular medical care).

        -  Step 9. Receive PBPC infusion (also known as autologous hematopoietic cell transplant,
           AHCT).

        -  Step 10. Within 3 days of AHCT (but typically 1 day), receive infusion of CpG-MCL
           Vaccine-primed T-cells, followed within 1 hour by a with 4th vaccination with CpG-MCL
           Vaccine (1st booster vaccination).

        -  Step 11. After hematopoietic recovery, receive 5th vaccination with CpG-MCl (2nd booster
           vaccination).

        -  Step 12. Monitor participants for general health and disease status through at least 3
           years.
    

Intervention name(s): CpG-MCL vaccine; PF-3512676; Vaccine-primed T-cells; Autologous hematopoietic stem cell transplant (HSCT); Rituximab; Standard induction chemotherapy; Cyclophosphamide; Filgrastim
Intervention type(s): Biological; Biological; Procedure; Procedure; Drug; Drug; Drug; Drug
Intervention description(s): CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.; PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. PF-03512676 acts as an agonist of human Toll-like receptor 9, leading to activation of antigen-presenting cells and a cascade of antitumor immune reactions.; Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.; Regular medical procedure; 375 mg/m² by infusion; Patient-specific, regular medical care treatment as determined by treating oncologist; Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC); Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
Other intervention name(s): CpG-activated, autologous tumor vaccine; Cytosine-Guanosine repeats (CpG)-mantle cell lymphoma (CpG-MCL vaccine); CPG-7909; Autologous peripheral blood progenitor cell (PBPC) transplant; Autologous peripheral blood stem cell (PBSC) transplant; Rituxan; hera; Cytoxtan; Neosar; CYT; CTX; CPM; G-CSF; Neupogen
Intervention MeSH terms: Cyclophosphamide; Rituximab; Vaccines
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment