Chemotherapy, Vaccine Therapy, and Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Combining chemotherapy with vaccine therapy and peripheral stem cell transplantation may be effective in treating multiple myeloma. PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy followed by vaccine therapy and peripheral stem cell transplantation in treating patients who have newly diagnosed multiple myeloma.

Detailed Description
-----------------
OBJECTIVES: Determine the efficacy of induction chemotherapy followed by autologous tumor cell vaccine and autologous peripheral blood stem cell transplantation in patients with multiple myeloma. Determine the safety of this regimen in these patients. OUTLINE: Autologous tumor cells are harvested. The vaccine is prepared in vitro by mixing autologous tumor cells with a bystander cell expressing sargramostim (GM-CSF). Patients receive induction chemotherapy followed by autologous tumor cell vaccination (ATCV) once. Patients then undergo autologous peripheral blood stem cell transplantation. At 6 weeks after transplantation, patients receive additional ATCVs every 3 weeks for a total of 8 vaccinations. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Official Title
-----------------
Vaccination In Peripheral Stem Cell Transplant Setting For Multiple Myeloma: The Use Of Autologous Tumor Cells/An Allo PSCT

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Biological: GVAX
* Procedure: Autologous transplant


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA Initial Presentation Age between 18 and 70 years ECOG 0 - 2 Patients with histologically confirmed multiple myeloma with ≥ 30% bone marrow involvement and a de novo presentation. One cycle of prior chemotherapy for myeloma is allowed. Local radiation therapy is permitted Ability to give informed consent No existing secondary malignancies and no history of secondary malignancies in the past 5 years (other than a history of carcinoma in situ of the cervix, superficial skin cancer, or superficial bladder cancer) No active autoimmune disease, nor a history of any autoimmune disease requiring medical treatment with systemic immunosuppressants No corticosteroids within 28 days of tumor harvest No major active medical or psychosocial problems that could be exacerbated or complicated by this treatment Not pregnant HIV negative AST/ALT, total bilirubin < threefold normal Absolute neutrophil count >500/mm3 Platelet count >30,000/mm3 Prior to Transplantation ECOG performance status of 0 - 2. No active/uncontrolled infection. Absolute neutrophil count (ANC) >1000/mm3. Platelet count >50,000/mm3. Hemoglobin >8g/dL AST/ALT, total bilirubin <3-fold normal. 50% or greater reduction in tumor burden with prior chemotherapy Patient has received a minimum of 2 cycles of an accepted induction chemotherapy regimen Patient fulfills the requirements for standard peripheral stem cell transplantation Prior to Posttransplant Vaccination No active/uncontrolled infection Absolute neutrophil count (ANC) >1000/mm3 Platelet count >50,000/mm3 Hemoglobin >8g/dL AST/ALT, total bilirubin <3-fold normal No unresolved Grade 3 or 4 adverse events related to the transplant EXCLUSION CRITERIA • Failure of autologous tumor-cell processing for vaccine production

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine<br>Participants are vaccinated with GVAX one month or more after finishing induction therapy (which is given as per standard of care). Two weeks later, participants go through leukapheresis on protocol, then receive autologous transplant as per standard of care. GVAX is administered eight subsequent times after the autologous transplant. | Biological: GVAX<br> <br> * Other names: Autologous tumor vaccine;Procedure: Autologous transplant<br> <br> * Other names: Auto SCT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor-specific immune response | Percentage of participants who had a delayed-type hypersensitivity reaction with induration greater than or equal to 5 millimeters to an intradermal injection of irradiated autologous tumor cells. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3-4 toxicity | Percentage of participants with grade 3-4 toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE 2.0). | Up to 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma