NCT00490529

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

Phase 1-2 Study of a CpG-Activated Whole Cell Vaccine Followed by Autologous "Immunotransplant" for Mantle Cell Lymphoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 59 (actual)
• Sponsor: Ronald Levy · Academic / Other
• Sex: All
• Age: 21 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lymphoma, Mantle-Cell

Interventions

Type	Name	Description
BIOLOGICAL	CpG-MCL vaccine	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.
BIOLOGICAL	PF-3512676	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.
PROCEDURE	Vaccine-primed T-cells	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.
PROCEDURE	Autologous hematopoietic stem cell transplant (HSCT)	Regular medical procedure
DRUG	Rituximab	375 mg/m² by infusion
DRUG	Standard induction chemotherapy	Patient-specific, regular medical care treatment as determined by treating oncologist
DRUG	Cyclophosphamide	Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
DRUG	Filgrastim	Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)

Timeline

• Start date: 2009-08-01
• Primary completion: 2017-12-14
• Completion: 2017-12-14
• First posted: 2007-06-22
• Last updated: 2020-01-13
• Results posted: 2020-01-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study