This randomized phase II trial studies how well vaccine therapy after donor stem cell transplant works in treating patients with myelodysplastic syndrome or acute myeloid leukemia that has spread to other places in the body (advanced). Vaccines made from a gene-modified virus and a person's tumor cells may help the body build an immune response to kill cancer cells. Giving chemotherapy before a donor peripheral blood or bone marrow transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. It is not yet known whether giving vaccine therapy after a donor peripheral blood or bone marrow transplant is more effective than transplant alone in treating myelodysplastic syndrome or acute myeloid leukemia.
Additional locations may be listed on ClinicalTrials.gov for NCT01773395.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. Progression-free survival (PFS) at 18 months after randomization.
SECONDARY OBJECTIVES:
I. To assess the safety of vaccination following allogeneic (ablative or reduced intensity) stem cell transplantation.
II. To assess incidence of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD), and chronic GVHD after vaccination following allogeneic stem cell transplantation.
III. To assess PFS after start of vaccination.
IV. To assess relapse and non-relapse mortality after vaccination.
V. To assess overall survival after vaccination.
VI. To assess biologic activity of irradiated, adenovirus vector transfected GM-CSF secreting autologous leukemia cell vaccination (GVAX) (autologous sargramostim [GM-CSF]-secreting lethally irradiated leukemia cell vaccine) as compared to placebo vaccination after hematopoietic stem cell transplantation (HSCT).
OUTLINE: Patients are randomized to 1 of 2 arms. Patients may receive cytoreductive therapy between harvest and transplant conditioning, at the discretion of the treating doctor.
CONDITIONING: All patients receive either reduced-intensity conditioning comprising fludarabine intravenously (IV) over 1 hour once daily (QD) and low-dose busulfan IV twice daily (BID) on days -5 to -2 (FluBu2) OR myeloablative conditioning comprising fludarabine IV over 1 hour QD and busulfan IV 4 times a day (QID) on days -5 to -2 (Flu/Bu4).
TRANSPLANT: All patients undergo donor peripheral blood stem cell (PBSC) or bone marrow (BM) transplant on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus orally (PO) BID starting on day –3 and continuing with taper one week after last vaccination for up to 9 months, and methotrexate IV on days 1, 3, 6, and 11.
ARM A: Within 30-60 days post-transplant, patients receive autologous GM-CSF-secreting lethally irradiated leukemia cell vaccine subcutaneously (SC) and intradermally (ID) weekly for 3 weeks and then every 2 weeks for 6 weeks for a total of 6 vaccinations.
ARM B: Within 30-60 days post-transplant, patients receive placebo vaccine SC and ID weekly for 3 weeks and then every 2 weeks for 6 weeks for a total of 6 vaccinations.
After completion of study treatment, patients are followed up for 15 years.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorVincent Trien-Vinh Ho