Phase I/II of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL

This study is currently recruiting participants.
Verified December 2012 by Stanford University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ronald Levy, Stanford University
ClinicalTrials.gov Identifier:
NCT00490529
First received: June 20, 2007
Last updated: December 29, 2012
Last verified: December 2012
  Purpose

While autologous hematopoietic stem cell transplant (AHCT) has been shown to cure some subtypes of non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL) still has a prognosis marked by relapse. This study will evaluate the safety and efficacy of treating newly diagnosed MCL patients with an autologous, tumor-derived vaccine followed by re-infusion of vaccine-primed T cells combined with standard autologous hematopoietic stem cell transplant (AHCT). CpG-MCL vaccine is derived from each patient's own tumor, treated in vitro with the immunostimulatory CpG-enriched oligodeoxynucleotide - PF-3512676 - and irradiated. The overall treatment schema is that patients receive: induction chemotherapy, priming vaccinations, leukapheresis to harvest vaccine-primed T cells, preparative myeloablative chemotherapy followed by AHCT, re-infusion of vaccine-primed T-cells ('immunotransplant') and repeat vaccinations zero and three months post-AHCT.


Condition Intervention Phase
Lymphoma, Mantle-Cell
Biological: CpG-MCL vaccine, primed T-cells
Procedure: Autologous peripheral blood stem cell transplantation
Procedure: CT scan
Procedure: PET-CT scan
Drug: PF-3512676
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of a CpG-Activated Whole Cell Vaccine Followed by Autologous "Immunotransplant" for Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • The primary endpoint of the trial is freedom from molecular residual disease (MRD) at the landmark of one-year post-transplant. [ Time Frame: Samples for MRD analysis are collected every 3 months until one-year post transplant. ] [ Designated as safety issue: No ]
    After the one-year mark, samples for MRD analysis will be collected every 6 months for 3 years or until disease progression.


Secondary Outcome Measures:
  • Secondary objectives are Time To Clinical Progression (TTP), and evaluation of anti-tumor immune responses after vaccination, and after immunotransplant. progression-free survival. [ Time Frame: 1 year, 3 years, 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 59
Study Start Date: August 2009
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: "CpG-MCL" vaccine
Patients will initially receive three 'priming' CpG-MCL vaccinations in 21 days at 4-7 day intervals, followed by collection of "primed" T-Cells. Subsequently, within 72 hours of autologous hematopoetic cell transplant (AHCT)(standard of care procedure), the patient will receive his/her CpG-MCL vaccine and reinfusion of primed T cells ("immunotransplant"). 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, primed T-cells
Other Name: CpG-activated, autologous tumor vaccine
Procedure: Autologous peripheral blood stem cell transplantation
Standard of Care
Other Name: Hematopoietic stem cell transplantation
Procedure: CT scan
Standard of Care
Other Name: X-ray computed tomography
Procedure: PET-CT scan
Standard of Care
Other Name: Poset emission tomography
Drug: PF-3512676
18 mg subcutaneous injection
Other Name: Pfizer
Drug: Rituximab
375 mg/m2 iv Standard of care.
Other Names:
  • Rituxan
  • MabThera

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be newly diagnosed with MCL, have an accessible disease site for excisional biopsy or sufficient peripheral blood tumor burden to safely leukapherese.
  • By standard clinical criteria be medically appropriate to receive induction chemotherapy and high-dose chemotherapy with AHCT.
  • Must be between 18 to 70 years of age.
  • Serum creatinine <2.0 or 24-hour creatinine clearance >60 ml/min.
  • Patients must be HIV negative.
  • ECOG performance status 0, 1, or 2.
  • Patients must be capable of signing an informed consent.

Exclusion Criteria:

  • Patients who are currently taking immunosuppressive medications.
  • Severe psychological or medical illness.
  • Patients may not be receiving any other investigational agents.
  • Pregnant or lactating women.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00490529

Contacts
Contact: Holbrook Kohrt, MD, PhD (650) 725-4968 kohrt@stanford.edu
Contact: Emily Troutner 650-725-4968 troutner@stanford.edu

Locations
United States, California
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Sub-Investigator: Holbrook Kohrt, MD, PhD         
Sub-Investigator: Ranjana Advani, MD         
Sub-Investigator: Robert Negrin, MD         
Sub-Investigator: David Miklos, MD, PhD         
Sub-Investigator: Wen Kai Weng, MD, PhD         
Sub-Investigator: Sally Arai, MD, PhD         
Sub-Investigator: Lauren Maeda, MD         
Sponsors and Collaborators
Ronald Levy
Investigators
Principal Investigator: Ronald Levy Stanford University
  More Information

Publications:
Responsible Party: Ronald Levy, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT00490529     History of Changes
Other Study ID Numbers: LYMNHL0040, 96940, LYMNHL0040-BMT212, 5089
Study First Received: June 20, 2007
Last Updated: December 29, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 16, 2014