Vaccine Study Now Underway

Vaccine Study Now Underway

A vaccine study jointly sponsored by the Liddy Shriver Sarcoma Initiative and the Brian Morden Foundation is now actively recrutiing patients. The study, "A pilot study of tumor lysate-pulsed dendritic cell vaccine for immune augmentation for high-risk solid tumor patients following autologous stem cell transplantation", is being conducted by James D. Geiger, M.D. (principal investigator) and John E. Levine, M.D. and Raymond J. Hutchinson, M.D. (co-investigators) and will take place at the University of Michigan. Patients with a histologically verified diagnosis of soft tissue sarcoma, including rhabdomyosarcoma, Ewing’s sarcoma family tumors (ES, PNET), synovial sarcoma, fibrosarcoma, or desmoplastic round cell tumor or neuroblastoma and Wilm’s tumor are potential candidates for this study. The details about it follow.

Trial Description

This pilot study will assess whether the experimental tumor vaccine can stimulate the immune system to fight cancer in addition to standard treatment. The study is being conducted primarily to determine the effectiveness of the vaccine to generate an immune response against the tumor, prolonging survival without tumor recurrence and to measure the side effects which occur in association with vaccine use. The study treatment will consist of high-dose chemotherapy followed by infusion of your own peripheral blood stem cells (PBSC) plus the administration of a series of three tumor vaccines.

Purpose

Chemotherapy drugs stop tumor cells from dividing so they stop growing or die. Peripheral blood stem cell transplantation allows the doctor to give higher doses of chemotherapy and thus kill more tumor cells. Dendritic cells are special white blood cells that can potentially stimulate the immune system to kill the remaining tumor cells. It is not yet known if giving dendritic cell tumor vaccines following stem cell transplantation will lead to a better immune response against the tumor.

This is a pilot study to evaluate the ability of tumor lysate-pulsed dendritic cell vaccines to augment the anti-tumor immune response in pediatric and young adult patients with solid tumors after autologous hematopoietic stem cell transplantation. The proposed study will further our understanding of immune responses to solid tumors and the ability of dendritic cell tumor vaccine to modulate the anti-tumor immune response in the post-hematopoietic stem cell transplant recovering immune system.

Eligibility

Eligibility criteria include the following:

Adequate tumor and peripheral blood stem cells are both needed to develop the vaccine and perform the autologous stem cell transplant. Tumor must be collected at the University of Michigan and processed fresh according to the protocol.

· Have a histologically verified diagnosis of neuroblastoma, Wilm’s tumor, or soft tissue sarcoma, including rhabdomyosarcoma, a Ewing’s sarcoma family tumor (ES, PNET), synovial sarcoma, fibrosarcoma, or desmoplastic round cell tumor.

· Meet one of the following criteria:

o Have metastatic disease at diagnosis

o Have never achieved complete remission following frontline standard therapy

o Have relapsed after receiving standard therapy.

· Less than 30 years of age at the time of original diagnosis.

· Have a source of tumor tissue from which approximately 1 gram of viable tumor can be obtained for vaccine development.

· Have a good performance status.

· Must have a life expectancy of at least 16 weeks.

· Females of child-bearing age (> 12 years old) must have a negative pregnancy test.

Patients may enroll on this study at various points in their treatment including diagnosis, recurrence, or just prior to initiation of study mandated transplant therapy. Because patients may enter this study prior to completion of pretransplant treatments, the below criteria must be met only in order to proceed to the high dose chemotherapy and autologous stem cell transplant of this study. These criteria are not a requirement to enter this study in order to collect tumor or peripheral blood stem cells.

	Must have achieved complete response or very good partial response (> 90% decrease in tumor volume) before proceeding to transplant.
	May have undergone prior autologous peripheral blood stem cell transplantation, provided at least 12 months have elapsed prior to entry on this study.
	Must have had a successful peripheral blood stem cell collection, with cryopreservation of PBSCs for both engraftment and for generation of dendritic cells.

Exclusion Criteria

	Patients who have received prior antitumor vaccines are ineligible.
	Patients who meet the response criteria but progress prior to study enrollment are ineligible.
	Patients with known autoimmune diseases or conditions are ineligible.
	Patients with HIV infection, AIDS, hepatitis B surface antigen positivity, ongoing bleeding, or any significant uncontrolled medical or psychiatric illness are ineligible.
	Prior allogenic transplant.
	Pregnant or nursing

Treatment / Intervention

Patients will have undergone successful collection of PBSCs for transplant engraftment and generation of dendritic cells. They will then undergo a high-dose chemotherapy conditioning regimen consisting of etoposide, thiotepa, and cyclophosphamide followed by hematopoietic stem cell transplant.

At approximately 28 days following transplant, patients will undergo an array of tests of immune function and start the tumor-pulsed dendritic cell vaccinations. The actual timing of the vaccinations will be based on when the individual patient first achieves a post-transplant absolute lymphocyte count of 200, for three consecutive days.

A series of three vaccinations will be administered to patients at two-week intervals (approximately days +28, +42, and +56). The vaccinations will be administered intradermally into the same arm or leg for all three vaccinations. This will be done on an outpatient basis. Patients will return 2 weeks, 6 weeks, and 12 weeks following their third vaccination (around days +70, +98, and +140) for an array of tests assessing general immune function and tumor-specific immune response and to undergo evaluation for tumor response.

Trial Contact Information Contact:

Cancer Answer Line 1-800-865-1125

Principal investigator, James D. Geiger, M.D.; Co-Investigators, John E. Levine, M.D. and Raymond J. Hutchinson, M.D.